[{"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"date_published":"2016-01-01T00:00:00Z","day":"01","year":"2016","publisher":"Nature Publishing Group","article_processing_charge":"No","_id":"1217","author":[{"first_name":"Vinatha","last_name":"Sreeramkumar","full_name":"Sreeramkumar, Vinatha"},{"last_name":"Hons","full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","first_name":"Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Carmen","full_name":"Punzón, Carmen","last_name":"Punzón"},{"last_name":"Stein","full_name":"Stein, Jens","first_name":"Jens"},{"first_name":"David","last_name":"Sancho","full_name":"Sancho, David"},{"full_name":"Fresno Forcelledo, Manuel","last_name":"Fresno Forcelledo","first_name":"Manuel"},{"full_name":"Cuesta, Natalia","last_name":"Cuesta","first_name":"Natalia"}],"status":"public","volume":94,"acknowledgement":"This manuscript has been supported by grants SAF2007-61716 and S-SAL-0159/2006 awarded by the Spanish Ministry of Science and Education and the Community of Madrid to Dr M Fresno.","publist_id":"6116","issue":"1","citation":{"ama":"Sreeramkumar V, Hons M, Punzón C, et al. Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and Cell Biology. 2016;94(1):39-51. doi:10.1038/icb.2015.62","ista":"Sreeramkumar V, Hons M, Punzón C, Stein J, Sancho D, Fresno Forcelledo M, Cuesta N. 2016. Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and Cell Biology. 94(1), 39–51.","apa":"Sreeramkumar, V., Hons, M., Punzón, C., Stein, J., Sancho, D., Fresno Forcelledo, M., & Cuesta, N. (2016). Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and Cell Biology. Nature Publishing Group. https://doi.org/10.1038/icb.2015.62","ieee":"V. Sreeramkumar et al., “Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors,” Immunology and Cell Biology, vol. 94, no. 1. Nature Publishing Group, pp. 39–51, 2016.","chicago":"Sreeramkumar, Vinatha, Miroslav Hons, Carmen Punzón, Jens Stein, David Sancho, Manuel Fresno Forcelledo, and Natalia Cuesta. “Efficient T-Cell Priming and Activation Requires Signaling through Prostaglandin E2 (EP) Receptors.” Immunology and Cell Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/icb.2015.62.","short":"V. Sreeramkumar, M. Hons, C. Punzón, J. Stein, D. Sancho, M. Fresno Forcelledo, N. Cuesta, Immunology and Cell Biology 94 (2016) 39–51.","mla":"Sreeramkumar, Vinatha, et al. “Efficient T-Cell Priming and Activation Requires Signaling through Prostaglandin E2 (EP) Receptors.” Immunology and Cell Biology, vol. 94, no. 1, Nature Publishing Group, 2016, pp. 39–51, doi:10.1038/icb.2015.62."},"quality_controlled":"1","type":"journal_article","language":[{"iso":"eng"}],"oa_version":"None","scopus_import":"1","date_updated":"2025-09-22T09:34:26Z","publication_status":"published","title":"Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors","abstract":[{"lang":"eng","text":"Understanding the regulation of T-cell responses during inflammation and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. In this regard, prostaglandin E 2 (PGE 2) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE 2 during T-cell receptor stimulation. In addition, we show that autocrine PGE 2 signaling through EP receptors is essential for optimal CD4 + T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE 2 was found to provide additive co-stimulatory signaling through AKT activation. Intravital multiphoton microscopy showed that triggering EP receptors in T cells is also essential for the stability of T cell-dendritic cell (DC) interactions and Th-cell accumulation in draining lymph nodes (LNs) during inflammation. We further demonstrated that blocking EP receptors in T cells during the initial phase of collagen-induced arthritis in mice resulted in a reduction of clinical arthritis. This could be attributable to defective T-cell activation, accompanied by a decline in activated and interferon-γ-producing CD4 + Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE 2, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE 2 signaling in T cells is also required for maintaining long and stable interactions with DCs within LNs. Blockade of EP receptors in vivo impairs T-cell activation and development of T cell-mediated inflammatory responses. This may have implications in various pathophysiological settings."}],"external_id":{"isi":["000367628600005"]},"doi":"10.1038/icb.2015.62","date_created":"2018-12-11T11:50:46Z","page":"39 - 51","publication":"Immunology and Cell Biology","month":"01","isi":1,"intvolume":" 94"},{"doi":"10.1146/annurev-cellbio-111315-125341","title":"Focal adhesion-independent cell migration","abstract":[{"text":"Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion-independent migration, and highlight the remaining open questions for the future.","lang":"eng"}],"external_id":{"isi":["000389576900019"]},"scopus_import":"1","date_updated":"2025-09-22T08:33:40Z","publication_status":"published","language":[{"iso":"eng"}],"oa_version":"None","intvolume":" 32","month":"10","isi":1,"date_created":"2018-12-11T11:51:08Z","publication":"Annual Review of Cell and Developmental Biology","page":"469 - 490","acknowledgement":"We would like to thank Dani Bodor for critical comments on the manuscript and Guillaume Salbreux for discussions. The authors are supported by the United Kingdom's Medical Research Council (MRC) (E.K.P. and I.M.A.; core funding to the MRC Laboratory for Molecular Cell Biology), by the European Research Council [ERC GA 311637 (E.K.P.) and ERC GA 281556 (M.S.)], and by a START award from the Austrian Science Foundation (M.S.).","publist_id":"6031","ec_funded":1,"status":"public","volume":32,"publisher":"Annual Reviews","_id":"1285","article_processing_charge":"No","author":[{"first_name":"Ewa","last_name":"Paluch","full_name":"Paluch, Ewa"},{"first_name":"Irene","last_name":"Aspalter","full_name":"Aspalter, Irene"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"department":[{"_id":"MiSi"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2016-10-06T00:00:00Z","day":"06","year":"2016","quality_controlled":"1","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7","grant_number":"281556"},{"call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"Y 564-B12"}],"type":"journal_article","citation":{"apa":"Paluch, E., Aspalter, I., & Sixt, M. K. (2016). Focal adhesion-independent cell migration. Annual Review of Cell and Developmental Biology. Annual Reviews. https://doi.org/10.1146/annurev-cellbio-111315-125341","ieee":"E. Paluch, I. Aspalter, and M. K. Sixt, “Focal adhesion-independent cell migration,” Annual Review of Cell and Developmental Biology, vol. 32. Annual Reviews, pp. 469–490, 2016.","short":"E. Paluch, I. Aspalter, M.K. Sixt, Annual Review of Cell and Developmental Biology 32 (2016) 469–490.","chicago":"Paluch, Ewa, Irene Aspalter, and Michael K Sixt. “Focal Adhesion-Independent Cell Migration.” Annual Review of Cell and Developmental Biology. Annual Reviews, 2016. https://doi.org/10.1146/annurev-cellbio-111315-125341.","ista":"Paluch E, Aspalter I, Sixt MK. 2016. Focal adhesion-independent cell migration. Annual Review of Cell and Developmental Biology. 32, 469–490.","ama":"Paluch E, Aspalter I, Sixt MK. Focal adhesion-independent cell migration. Annual Review of Cell and Developmental Biology. 2016;32:469-490. doi:10.1146/annurev-cellbio-111315-125341","mla":"Paluch, Ewa, et al. “Focal Adhesion-Independent Cell Migration.” Annual Review of Cell and Developmental Biology, vol. 32, Annual Reviews, 2016, pp. 469–90, doi:10.1146/annurev-cellbio-111315-125341."}},{"issue":"7","has_accepted_license":"1","type":"journal_article","quality_controlled":"1","citation":{"mla":"Russo, Erica, et al. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels.” Cell Reports, vol. 14, no. 7, Cell Press, 2016, pp. 1723–34, doi:10.1016/j.celrep.2016.01.048.","apa":"Russo, E., Teijeira, A., Vaahtomeri, K., Willrodt, A., Bloch, J., Nitschké, M., … Halin, C. (2016). Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.01.048","ieee":"E. Russo et al., “Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels,” Cell Reports, vol. 14, no. 7. Cell Press, pp. 1723–1734, 2016.","chicago":"Russo, Erica, Alvaro Teijeira, Kari Vaahtomeri, Ann Willrodt, Joël Bloch, Maximilian Nitschké, Laura Santambrogio, Dontscho Kerjaschki, Michael K Sixt, and Cornelia Halin. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels.” Cell Reports. Cell Press, 2016. https://doi.org/10.1016/j.celrep.2016.01.048.","short":"E. Russo, A. Teijeira, K. Vaahtomeri, A. Willrodt, J. Bloch, M. Nitschké, L. Santambrogio, D. Kerjaschki, M.K. Sixt, C. Halin, Cell Reports 14 (2016) 1723–1734.","ama":"Russo E, Teijeira A, Vaahtomeri K, et al. Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels. Cell Reports. 2016;14(7):1723-1734. doi:10.1016/j.celrep.2016.01.048","ista":"Russo E, Teijeira A, Vaahtomeri K, Willrodt A, Bloch J, Nitschké M, Santambrogio L, Kerjaschki D, Sixt MK, Halin C. 2016. Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels. Cell Reports. 14(7), 1723–1734."},"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publisher":"Cell Press","_id":"1490","article_processing_charge":"No","author":[{"first_name":"Erica","full_name":"Russo, Erica","last_name":"Russo"},{"full_name":"Teijeira, Alvaro","last_name":"Teijeira","first_name":"Alvaro"},{"full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri","id":"368EE576-F248-11E8-B48F-1D18A9856A87","first_name":"Kari","orcid":"0000-0001-7829-3518"},{"first_name":"Ann","last_name":"Willrodt","full_name":"Willrodt, Ann"},{"full_name":"Bloch, Joël","last_name":"Bloch","first_name":"Joël"},{"full_name":"Nitschké, Maximilian","last_name":"Nitschké","first_name":"Maximilian"},{"first_name":"Laura","last_name":"Santambrogio","full_name":"Santambrogio, Laura"},{"last_name":"Kerjaschki","full_name":"Kerjaschki, Dontscho","first_name":"Dontscho"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"},{"last_name":"Halin","full_name":"Halin, Cornelia","first_name":"Cornelia"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"year":"2016","day":"23","date_published":"2016-02-23T00:00:00Z","pubrep_id":"515","publist_id":"5697","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file":[{"date_updated":"2020-07-14T12:44:58Z","access_level":"open_access","file_size":5489897,"date_created":"2018-12-12T10:12:30Z","creator":"system","checksum":"c98c1151d5f1e5ce1643a83d8d7f3c29","file_name":"IST-2016-515-v1+1_1-s2.0-S2211124716300262-main.pdf","content_type":"application/pdf","relation":"main_file","file_id":"4948"}],"status":"public","file_date_updated":"2020-07-14T12:44:58Z","volume":14,"ddc":["570"],"isi":1,"month":"02","page":"1723 - 1734","publication":"Cell Reports","date_created":"2018-12-11T11:52:19Z","oa":1,"intvolume":" 14","scopus_import":"1","publication_status":"published","date_updated":"2025-09-18T11:16:44Z","oa_version":"Published Version","language":[{"iso":"eng"}],"doi":"10.1016/j.celrep.2016.01.048","abstract":[{"lang":"eng","text":"To induce adaptive immunity, dendritic cells (DCs) migrate through afferent lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively crawl into downstream collecting vessels. From there, they are next passively and rapidly transported to the dLN by lymph flow. Here, we describe a role for the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial monolayers, thereby inducing downstream-directed DC migration. These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient."}],"title":"Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels","external_id":{"isi":["000370970200016"]}},{"issue":"12","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400263","open_access":"1"}],"citation":{"mla":"Salzer, Elisabeth, et al. “RASGRP1 Deficiency Causes Immunodeficiency with Impaired Cytoskeletal Dynamics.” Nature Immunology, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1352–60, doi:10.1038/ni.3575.","ama":"Salzer E, Çaǧdaş D, Hons M, et al. RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature Immunology. 2016;17(12):1352-1360. doi:10.1038/ni.3575","ista":"Salzer E, Çaǧdaş D, Hons M, Mace E, Garncarz W, Petronczki O, Platzer R, Pfajfer L, Bilic I, Ban S, Willmann K, Mukherjee M, Supper V, Hsu H, Banerjee P, Sinha P, Mcclanahan F, Zlabinger G, Pickl W, Gribben J, Stockinger H, Bennett K, Huppa J, Dupré L, Sanal Ö, Jäger U, Sixt MK, Tezcan I, Orange J, Boztug K. 2016. RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature Immunology. 17(12), 1352–1360.","chicago":"Salzer, Elisabeth, Deniz Çaǧdaş, Miroslav Hons, Emily Mace, Wojciech Garncarz, Oezlem Petronczki, René Platzer, et al. “RASGRP1 Deficiency Causes Immunodeficiency with Impaired Cytoskeletal Dynamics.” Nature Immunology. Nature Publishing Group, 2016. https://doi.org/10.1038/ni.3575.","short":"E. Salzer, D. Çaǧdaş, M. Hons, E. Mace, W. Garncarz, O. Petronczki, R. Platzer, L. Pfajfer, I. Bilic, S. Ban, K. Willmann, M. Mukherjee, V. Supper, H. Hsu, P. Banerjee, P. Sinha, F. Mcclanahan, G. Zlabinger, W. Pickl, J. Gribben, H. Stockinger, K. Bennett, J. Huppa, L. Dupré, Ö. Sanal, U. Jäger, M.K. Sixt, I. Tezcan, J. Orange, K. Boztug, Nature Immunology 17 (2016) 1352–1360.","apa":"Salzer, E., Çaǧdaş, D., Hons, M., Mace, E., Garncarz, W., Petronczki, O., … Boztug, K. (2016). RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3575","ieee":"E. Salzer et al., “RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics,” Nature Immunology, vol. 17, no. 12. Nature Publishing Group, pp. 1352–1360, 2016."},"article_type":"original","quality_controlled":"1","type":"journal_article","pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"date_published":"2016-12-01T00:00:00Z","day":"01","year":"2016","publisher":"Nature Publishing Group","_id":"1137","article_processing_charge":"No","author":[{"first_name":"Elisabeth","full_name":"Salzer, Elisabeth","last_name":"Salzer"},{"full_name":"Çaǧdaş, Deniz","last_name":"Çaǧdaş","first_name":"Deniz"},{"first_name":"Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav","last_name":"Hons"},{"first_name":"Emily","last_name":"Mace","full_name":"Mace, Emily"},{"full_name":"Garncarz, Wojciech","last_name":"Garncarz","first_name":"Wojciech"},{"first_name":"Oezlem","full_name":"Petronczki, Oezlem","last_name":"Petronczki"},{"full_name":"Platzer, René","last_name":"Platzer","first_name":"René"},{"first_name":"Laurène","full_name":"Pfajfer, Laurène","last_name":"Pfajfer"},{"full_name":"Bilic, Ivan","last_name":"Bilic","first_name":"Ivan"},{"first_name":"Sol","last_name":"Ban","full_name":"Ban, Sol"},{"first_name":"Katharina","full_name":"Willmann, Katharina","last_name":"Willmann"},{"full_name":"Mukherjee, Malini","last_name":"Mukherjee","first_name":"Malini"},{"first_name":"Verena","full_name":"Supper, Verena","last_name":"Supper"},{"first_name":"Hsiangting","last_name":"Hsu","full_name":"Hsu, Hsiangting"},{"first_name":"Pinaki","full_name":"Banerjee, Pinaki","last_name":"Banerjee"},{"full_name":"Sinha, Papiya","last_name":"Sinha","first_name":"Papiya"},{"first_name":"Fabienne","last_name":"Mcclanahan","full_name":"Mcclanahan, Fabienne"},{"full_name":"Zlabinger, Gerhard","last_name":"Zlabinger","first_name":"Gerhard"},{"last_name":"Pickl","full_name":"Pickl, Winfried","first_name":"Winfried"},{"last_name":"Gribben","full_name":"Gribben, John","first_name":"John"},{"last_name":"Stockinger","full_name":"Stockinger, Hannes","first_name":"Hannes"},{"last_name":"Bennett","full_name":"Bennett, Keiryn","first_name":"Keiryn"},{"first_name":"Johannes","full_name":"Huppa, Johannes","last_name":"Huppa"},{"last_name":"Dupré","full_name":"Dupré, Loï̈C","first_name":"Loï̈C"},{"full_name":"Sanal, Özden","last_name":"Sanal","first_name":"Özden"},{"first_name":"Ulrich","last_name":"Jäger","full_name":"Jäger, Ulrich"},{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"},{"first_name":"Ilhan","full_name":"Tezcan, Ilhan","last_name":"Tezcan"},{"last_name":"Orange","full_name":"Orange, Jordan","first_name":"Jordan"},{"full_name":"Boztug, Kaan","last_name":"Boztug","first_name":"Kaan"}],"status":"public","volume":17,"publist_id":"6221","date_created":"2018-12-11T11:50:21Z","page":"1352 - 1360","publication":"Nature Immunology","month":"12","isi":1,"intvolume":" 17","oa":1,"language":[{"iso":"eng"}],"oa_version":"Submitted Version","scopus_import":"1","date_updated":"2025-09-22T14:13:22Z","publication_status":"published","abstract":[{"text":"RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1. RASGRP1 deficiency also resulted in defective proliferation, activation and motility of T cells and B cells. RASGRP1-deficient natural killer (NK) cells exhibited impaired cytotoxicity with defective granule convergence and actin accumulation. Interaction proteomics identified the dynein light chain DYNLL1 as interacting with RASGRP1, which links RASGRP1 to cytoskeletal dynamics. RASGRP1-deficient cells showed decreased activation of the GTPase RhoA. Treatment with lenalidomide increased RhoA activity and reversed the migration and activation defects of RASGRP1-deficient lymphocytes.","lang":"eng"}],"title":"RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics","external_id":{"isi":["000388056400005"],"pmid":["27776107"]},"doi":"10.1038/ni.3575"},{"day":"01","year":"2016","date_published":"2016-12-01T00:00:00Z","department":[{"_id":"MiSi"},{"_id":"PeJo"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","_id":"1142","author":[{"first_name":"Rui","full_name":"Martins, Rui","last_name":"Martins"},{"first_name":"Julia","last_name":"Maier","full_name":"Maier, Julia"},{"first_name":"Anna","full_name":"Gorki, Anna","last_name":"Gorki"},{"first_name":"Kilian","last_name":"Huber","full_name":"Huber, Kilian"},{"full_name":"Sharif, Omar","last_name":"Sharif","first_name":"Omar"},{"first_name":"Philipp","full_name":"Starkl, Philipp","last_name":"Starkl"},{"first_name":"Simona","full_name":"Saluzzo, Simona","last_name":"Saluzzo"},{"last_name":"Quattrone","full_name":"Quattrone, Federica","first_name":"Federica"},{"last_name":"Gawish","full_name":"Gawish, Riem","first_name":"Riem"},{"last_name":"Lakovits","full_name":"Lakovits, Karin","first_name":"Karin"},{"first_name":"Michael","last_name":"Aichinger","full_name":"Aichinger, Michael"},{"last_name":"Radic Sarikas","full_name":"Radic Sarikas, Branka","first_name":"Branka"},{"first_name":"Charles","full_name":"Lardeau, Charles","last_name":"Lardeau"},{"first_name":"Anastasiya","last_name":"Hladik","full_name":"Hladik, Anastasiya"},{"last_name":"Korosec","full_name":"Korosec, Ana","first_name":"Ana"},{"full_name":"Brown, Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus"},{"first_name":"Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7829-3518","full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri"},{"id":"2EDEA62C-F248-11E8-B48F-1D18A9856A87","first_name":"Michelle","last_name":"Duggan","full_name":"Duggan, Michelle"},{"last_name":"Kerjaschki","full_name":"Kerjaschki, Dontscho","first_name":"Dontscho"},{"full_name":"Esterbauer, Harald","last_name":"Esterbauer","first_name":"Harald"},{"first_name":"Jacques","last_name":"Colinge","full_name":"Colinge, Jacques"},{"first_name":"Stephanie","last_name":"Eisenbarth","full_name":"Eisenbarth, Stephanie"},{"first_name":"Thomas","full_name":"Decker, Thomas","last_name":"Decker"},{"full_name":"Bennett, Keiryn","last_name":"Bennett","first_name":"Keiryn"},{"first_name":"Stefan","last_name":"Kubicek","full_name":"Kubicek, Stefan"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"},{"first_name":"Giulio","last_name":"Superti Furga","full_name":"Superti Furga, Giulio"},{"full_name":"Knapp, Sylvia","last_name":"Knapp","first_name":"Sylvia"}],"article_processing_charge":"No","publisher":"Nature Publishing Group","volume":17,"status":"public","publist_id":"6216","acknowledgement":"Y. Fukui (Medical Institute of Bioregulation, Kyushu University) and J. Stein (Theodor Kocher Institute, University of Bern) are acknowledged for providing the DOCK8 deficient bone marrow. and H. Häcker (St. Judes Children's Research Hospital) for providing the ERHBD-HoxB8-encoding retroviral construct. pSpCas9(BB)-2a-Puro (PX459) was a gift from F. Zhang (Massachusetts Institute of Technology) (Addgene plasmid # 48139) and pGRG36 was a gift from N. Craig (Johns Hopkins University School of Medicine) (Addgene plasmid # 16666). LifeAct-GFP-encoding retrovirus was kindly provided by A. Leithner (Institute of Science and Technology Austria). pSIM8 and TKC E. coli were gifts from D.L. Court (Center for Cancer Research, National Cancer Institute). We acknowledge M. Gröger and S. Rauscher for excellent technical support (Core imaging facility, Medical University of Vienna). We thank D.P. Barlow and L.R. Cheever for critical reading of the manuscript. This work was supported by the Austrian Academy of Sciences, the Science Fund of the Austrian National Bank (14107) and the Austrian Science Fund FWF (I1620-B22) in the Infect-ERA framework (to S.Knapp).","issue":"12","main_file_link":[{"url":"https://ora.ox.ac.uk/objects/uuid:f53a464e-1e5b-4f08-a7d8-b6749b852b9d","open_access":"1"}],"citation":{"mla":"Martins, Rui, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” Nature Immunology, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1361–72, doi:10.1038/ni.3590.","ista":"Martins R, Maier J, Gorki A, Huber K, Sharif O, Starkl P, Saluzzo S, Quattrone F, Gawish R, Lakovits K, Aichinger M, Radic Sarikas B, Lardeau C, Hladik A, Korosec A, Brown M, Vaahtomeri K, Duggan M, Kerjaschki D, Esterbauer H, Colinge J, Eisenbarth S, Decker T, Bennett K, Kubicek S, Sixt MK, Superti Furga G, Knapp S. 2016. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. 17(12), 1361–1372.","ama":"Martins R, Maier J, Gorki A, et al. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. 2016;17(12):1361-1372. doi:10.1038/ni.3590","short":"R. Martins, J. Maier, A. Gorki, K. Huber, O. Sharif, P. Starkl, S. Saluzzo, F. Quattrone, R. Gawish, K. Lakovits, M. Aichinger, B. Radic Sarikas, C. Lardeau, A. Hladik, A. Korosec, M. Brown, K. Vaahtomeri, M. Duggan, D. Kerjaschki, H. Esterbauer, J. Colinge, S. Eisenbarth, T. Decker, K. Bennett, S. Kubicek, M.K. Sixt, G. Superti Furga, S. Knapp, Nature Immunology 17 (2016) 1361–1372.","chicago":"Martins, Rui, Julia Maier, Anna Gorki, Kilian Huber, Omar Sharif, Philipp Starkl, Simona Saluzzo, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” Nature Immunology. Nature Publishing Group, 2016. https://doi.org/10.1038/ni.3590.","apa":"Martins, R., Maier, J., Gorki, A., Huber, K., Sharif, O., Starkl, P., … Knapp, S. (2016). Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3590","ieee":"R. Martins et al., “Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions,” Nature Immunology, vol. 17, no. 12. Nature Publishing Group, pp. 1361–1372, 2016."},"type":"journal_article","quality_controlled":"1","oa_version":"Submitted Version","language":[{"iso":"eng"}],"publication_status":"published","date_updated":"2025-09-22T14:10:50Z","scopus_import":"1","external_id":{"isi":["000388056400006"]},"abstract":[{"text":"Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders.","lang":"eng"}],"title":"Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions","doi":"10.1038/ni.3590","page":"1361 - 1372","publication":"Nature Immunology","date_created":"2018-12-11T11:50:22Z","isi":1,"month":"12","intvolume":" 17","oa":1},{"acknowledgement":"This work was supported by the Boehringer Ingelheim Fonds, the European Research Council (ERC StG 281556), and a START Award of the Austrian Science Foundation (FWF). We thank Robert Hauschild, Anne Reversat, and Jack Merrin for valuable input and the Imaging Facility of IST Austria for excellent support.","publist_id":"5573","ec_funded":1,"status":"public","volume":570,"publisher":"Elsevier","article_processing_charge":"No","_id":"1597","author":[{"first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","last_name":"Schwarz"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"department":[{"_id":"MiSi"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2016-01-01T00:00:00Z","day":"01","year":"2016","quality_controlled":"1","project":[{"grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7"},{"grant_number":"Y 564-B12","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"}],"type":"journal_article","pmid":1,"citation":{"mla":"Schwarz, Jan, and Michael K. Sixt. “Quantitative Analysis of Dendritic Cell Haptotaxis.” Methods in Enzymology, vol. 570, Elsevier, 2016, pp. 567–81, doi:10.1016/bs.mie.2015.11.004.","ista":"Schwarz J, Sixt MK. 2016. Quantitative analysis of dendritic cell haptotaxis. Methods in Enzymology. 570, 567–581.","ama":"Schwarz J, Sixt MK. Quantitative analysis of dendritic cell haptotaxis. Methods in Enzymology. 2016;570:567-581. doi:10.1016/bs.mie.2015.11.004","short":"J. Schwarz, M.K. Sixt, Methods in Enzymology 570 (2016) 567–581.","chicago":"Schwarz, Jan, and Michael K Sixt. “Quantitative Analysis of Dendritic Cell Haptotaxis.” Methods in Enzymology. Elsevier, 2016. https://doi.org/10.1016/bs.mie.2015.11.004.","apa":"Schwarz, J., & Sixt, M. K. (2016). Quantitative analysis of dendritic cell haptotaxis. Methods in Enzymology. Elsevier. https://doi.org/10.1016/bs.mie.2015.11.004","ieee":"J. Schwarz and M. K. Sixt, “Quantitative analysis of dendritic cell haptotaxis,” Methods in Enzymology, vol. 570. Elsevier, pp. 567–581, 2016."},"article_type":"original","doi":"10.1016/bs.mie.2015.11.004","acknowledged_ssus":[{"_id":"Bio"}],"abstract":[{"text":"Chemokines are the main guidance cues directing leukocyte migration. Opposed to early assumptions, chemokines do not necessarily act as soluble cues but are often immobilized within tissues, e.g., dendritic cell migration toward lymphatic vessels is guided by a haptotactic gradient of the chemokine CCL21. Controlled assay systems to quantitatively study haptotaxis in vitro are still missing. In this chapter, we describe an in vitro haptotaxis assay optimized for the unique properties of dendritic cells. The chemokine CCL21 is immobilized in a bioactive state, using laser-assisted protein adsorption by photobleaching. The cells follow this immobilized CCL21 gradient in a haptotaxis chamber, which provides three dimensionally confined migration conditions.","lang":"eng"}],"title":"Quantitative analysis of dendritic cell haptotaxis","external_id":{"isi":["000375648700025"],"pmid":["26921962"]},"scopus_import":"1","date_updated":"2025-09-18T11:02:13Z","publication_status":"published","language":[{"iso":"eng"}],"oa_version":"None","intvolume":" 570","month":"01","isi":1,"corr_author":"1","date_created":"2018-12-11T11:52:56Z","page":"567 - 581","publication":"Methods in Enzymology"},{"intvolume":" 351","oa":1,"date_created":"2018-12-11T11:52:57Z","publication":"Science","page":"186 - 190","month":"01","isi":1,"corr_author":"1","title":"Polysialylation controls dendritic cell trafficking by regulating chemokine recognition","acknowledged_ssus":[{"_id":"SSU"}],"abstract":[{"text":"The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.\r\n","lang":"eng"}],"external_id":{"pmid":["26657283"],"isi":["000367806500045"]},"doi":"10.1126/science.aad0512","language":[{"iso":"eng"}],"oa_version":"Submitted Version","scopus_import":"1","publication_status":"published","date_updated":"2025-09-18T11:01:30Z","citation":{"ieee":"E. Kiermaier et al., “Polysialylation controls dendritic cell trafficking by regulating chemokine recognition,” Science, vol. 351, no. 6269. American Association for the Advancement of Science, pp. 186–190, 2016.","apa":"Kiermaier, E., Moussion, C., Veldkamp, C., Gerardy Schahn, R., de Vries, I., Williams, L., … Sixt, M. K. (2016). Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aad0512","chicago":"Kiermaier, Eva, Christine Moussion, Christopher Veldkamp, Rita Gerardy Schahn, Ingrid de Vries, Larry Williams, Gary Chaffee, et al. “Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aad0512.","short":"E. Kiermaier, C. Moussion, C. Veldkamp, R. Gerardy Schahn, I. de Vries, L. Williams, G. Chaffee, A. Phillips, F. Freiberger, R. Imre, D. Taleski, R. Payne, A. Braun, R. Förster, K. Mechtler, M. Mühlenhoff, B. Volkman, M.K. Sixt, Science 351 (2016) 186–190.","ama":"Kiermaier E, Moussion C, Veldkamp C, et al. Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. 2016;351(6269):186-190. doi:10.1126/science.aad0512","ista":"Kiermaier E, Moussion C, Veldkamp C, Gerardy Schahn R, de Vries I, Williams L, Chaffee G, Phillips A, Freiberger F, Imre R, Taleski D, Payne R, Braun A, Förster R, Mechtler K, Mühlenhoff M, Volkman B, Sixt MK. 2016. Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. 351(6269), 186–190.","mla":"Kiermaier, Eva, et al. “Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science, vol. 351, no. 6269, American Association for the Advancement of Science, 2016, pp. 186–90, doi:10.1126/science.aad0512."},"article_type":"original","quality_controlled":"1","project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556"},{"grant_number":"289720","call_identifier":"FP7","_id":"25A76F58-B435-11E9-9278-68D0E5697425","name":"Stromal Cell-immune Cell Interactions in Health and Disease"},{"grant_number":"Y 564-B12","call_identifier":"FWF","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"type":"journal_article","pmid":1,"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/"}],"issue":"6269","status":"public","ec_funded":1,"volume":351,"acknowledgement":"We thank S. Schüchner and E. Ogris for kindly providing the antibody to GFP, M. Helmbrecht and A. Huber for providing Nrp2−/− mice, the IST Scientific Support Facilities for excellent services, and J. Renkawitz and K. Vaahtomeri for critically reading the manuscript. ","publist_id":"5570","department":[{"_id":"MiSi"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2016-01-08T00:00:00Z","day":"08","year":"2016","publisher":"American Association for the Advancement of Science","author":[{"last_name":"Kiermaier","full_name":"Kiermaier, Eva","orcid":"0000-0001-6165-5738","first_name":"Eva","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christine","id":"3356F664-F248-11E8-B48F-1D18A9856A87","full_name":"Moussion, Christine","last_name":"Moussion"},{"first_name":"Christopher","full_name":"Veldkamp, Christopher","last_name":"Veldkamp"},{"last_name":"Gerardy Schahn","full_name":"Gerardy Schahn, Rita","first_name":"Rita"},{"last_name":"De Vries","full_name":"De Vries, Ingrid","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Larry","full_name":"Williams, Larry","last_name":"Williams"},{"last_name":"Chaffee","full_name":"Chaffee, Gary","first_name":"Gary"},{"first_name":"Andrew","last_name":"Phillips","full_name":"Phillips, Andrew"},{"first_name":"Friedrich","last_name":"Freiberger","full_name":"Freiberger, Friedrich"},{"first_name":"Richard","full_name":"Imre, Richard","last_name":"Imre"},{"first_name":"Deni","full_name":"Taleski, Deni","last_name":"Taleski"},{"last_name":"Payne","full_name":"Payne, Richard","first_name":"Richard"},{"first_name":"Asolina","full_name":"Braun, Asolina","last_name":"Braun"},{"first_name":"Reinhold","full_name":"Förster, Reinhold","last_name":"Förster"},{"last_name":"Mechtler","full_name":"Mechtler, Karl","first_name":"Karl"},{"full_name":"Mühlenhoff, Martina","last_name":"Mühlenhoff","first_name":"Martina"},{"last_name":"Volkman","full_name":"Volkman, Brian","first_name":"Brian"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"_id":"1599","article_processing_charge":"No"},{"oa":1,"supervisor":[{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"corr_author":"1","ddc":["570"],"month":"07","page":"178","date_created":"2018-12-11T11:50:18Z","OA_place":"publisher","degree_awarded":"PhD","title":"Quantitative analysis of haptotactic cell migration","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"abstract":[{"lang":"eng","text":"Directed cell migration is a hallmark feature, present in almost all multi-cellular\r\norganisms. Despite its importance, basic questions regarding force transduction\r\nor directional sensing are still heavily investigated. Directed migration of cells\r\nguided by immobilized guidance cues - haptotaxis - occurs in key-processes,\r\nsuch as embryonic development and immunity (Middleton et al., 1997; Nguyen\r\net al., 2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues\r\ncomprise adhesive ligands, such as collagen and fibronectin (Barczyk et al.,\r\n2009), or chemokines - the main guidance cues for migratory leukocytes\r\n(Middleton et al., 1997; Weber et al., 2013). While adhesive ligands serve as\r\nattachment sites guiding cell migration (Carter, 1965), chemokines instruct\r\nhaptotactic migration by inducing adhesion to adhesive ligands and directional\r\nguidance (Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis\r\nof the cellular response to immobilized guidance cues requires in vitro assays\r\nthat foster cell migration, offer accurate control of the immobilized cues on a\r\nsubcellular scale and in the ideal case closely reproduce in vivo conditions. The\r\nexploration of haptotactic cell migration through design and employment of such\r\nassays represents the main focus of this work.\r\nDendritic cells (DCs) are leukocytes, which after encountering danger\r\nsignals such as pathogens in peripheral organs instruct naïve T-cells and\r\nconsequently the adaptive immune response in the lymph node (Mellman and\r\nSteinman, 2001). To reach the lymph node from the periphery, DCs follow\r\nhaptotactic gradients of the chemokine CCL21 towards lymphatic vessels\r\n(Weber et al., 2013). Questions about how DCs interpret haptotactic CCL21\r\ngradients have not yet been addressed. The main reason for this is the lack of\r\nan assay that offers diverse haptotactic environments, hence allowing the study\r\nof DC migration as a response to different signals of immobilized guidance cue.\r\nIn this work, we developed an in vitro assay that enables us to\r\nquantitatively assess DC haptotaxis, by combining precisely controllable\r\nchemokine photo-patterning with physically confining migration conditions. With this tool at hand, we studied the influence of CCL21 gradient properties and\r\nconcentration on DC haptotaxis. We found that haptotactic gradient sensing\r\ndepends on the absolute CCL21 concentration in combination with the local\r\nsteepness of the gradient. Our analysis suggests that the directionality of\r\nmigrating DCs is governed by the signal-to-noise ratio of CCL21 binding to its\r\nreceptor CCR7. Moreover, the haptotactic CCL21 gradient formed in vivo\r\nprovides an optimal shape for DCs to recognize haptotactic guidance cue.\r\nBy reconstitution of the CCL21 gradient in vitro we were also able to\r\nstudy the influence of CCR7 signal termination on DC haptotaxis. To this end,\r\nwe used DCs lacking the G-protein coupled receptor kinase GRK6, which is\r\nresponsible for CCL21 induced CCR7 receptor phosphorylation and\r\ndesensitization (Zidar et al., 2009). We found that CCR7 desensitization by\r\nGRK6 is crucial for maintenance of haptotactic CCL21 gradient sensing in vitro\r\nand confirm those observations in vivo.\r\nIn the context of the organism, immobilized haptotactic guidance cues\r\noften coincide and compete with soluble chemotactic guidance cues. During\r\nwound healing, fibroblasts are exposed and influenced by adhesive cues and\r\nsoluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly,\r\nmigrating DCs are exposed to both, soluble chemokines (CCL19 and truncated\r\nCCL21) inducing chemotactic behavior as well as the immobilized CCL21. To\r\nquantitatively assess these complex coinciding immobilized and soluble\r\nguidance cues, we implemented our chemokine photo-patterning technique in a\r\nmicrofluidic system allowing for chemotactic gradient generation. To validate\r\nthe assay, we observed DC migration in competing CCL19/CCL21\r\nenvironments.\r\nAdhesiveness guided haptotaxis has been studied intensively over the\r\nlast century. However, quantitative studies leading to conceptual models are\r\nlargely missing, again due to the lack of a precisely controllable in vitro assay. A\r\nrequirement for such an in vitro assay is that it must prevent any uncontrolled\r\ncell adhesion. This can be accomplished by stable passivation of the surface. In\r\naddition, controlled adhesion must be sustainable, quantifiable and dose\r\ndependent in order to create homogenous gradients. Therefore, we developed a novel covalent photo-patterning technique satisfying all these needs. In\r\ncombination with a sustainable poly-vinyl alcohol (PVA) surface coating we\r\nwere able to generate gradients of adhesive cue to direct cell migration. This\r\napproach allowed us to characterize the haptotactic migratory behavior of\r\nzebrafish keratocytes in vitro. Furthermore, defined patterns of adhesive cue\r\nallowed us to control for cell shape and growth on a subcellular scale."}],"date_updated":"2026-04-08T14:28:53Z","publication_status":"published","oa_version":"Published Version","language":[{"iso":"eng"}],"type":"dissertation","citation":{"mla":"Schwarz, Jan. Quantitative Analysis of Haptotactic Cell Migration. Institute of Science and Technology Austria, 2016.","ista":"Schwarz J. 2016. Quantitative analysis of haptotactic cell migration. Institute of Science and Technology Austria.","ama":"Schwarz J. Quantitative analysis of haptotactic cell migration. 2016.","chicago":"Schwarz, Jan. “Quantitative Analysis of Haptotactic Cell Migration.” Institute of Science and Technology Austria, 2016.","short":"J. Schwarz, Quantitative Analysis of Haptotactic Cell Migration, Institute of Science and Technology Austria, 2016.","ieee":"J. Schwarz, “Quantitative analysis of haptotactic cell migration,” Institute of Science and Technology Austria, 2016.","apa":"Schwarz, J. (2016). Quantitative analysis of haptotactic cell migration. Institute of Science and Technology Austria."},"publication_identifier":{"issn":["2663-337X"]},"has_accepted_license":"1","publist_id":"6231","acknowledgement":"First, I would like to thank Michael Sixt for being a great supervisor, mentor and\r\nscientist. I highly appreciate his guidance and continued support. Furthermore, I\r\nam very grateful that he gave me the exceptional opportunity to pursue many\r\nideas of which some managed to be included in this thesis.\r\nI owe sincere thanks to the members of my PhD thesis committee, Daria\r\nSiekhaus, Daniel Legler and Harald Janovjak. Especially I would like to thank\r\nDaria for her advice and encouragement during our regular progress meetings.\r\nI also want to thank the team and fellows of the Boehringer Ingelheim Fond\r\n(BIF) PhD Fellowship for amazing and inspiring meetings and the BIF for\r\nfinancial support.\r\nImportant factors for the success of this thesis were the warm, creative\r\nand helpful atmosphere as well as the team spirit of the whole Sixt Lab.\r\nTherefore I would like to thank my current and former colleagues Frank Assen,\r\nMarkus Brown, Ingrid de Vries, Michelle Duggan, Alexander Eichner, Miroslav\r\nHons, Eva Kiermaier, Aglaja Kopf, Alexander Leithner, Christine Moussion, Jan\r\nMüller, Maria Nemethova, Jörg Renkawitz, Anne Reversat, Kari Vaahtomeri,\r\nMichele Weber and Stefan Wieser. We had an amazing time with many\r\nlegendary evenings and events. Along these lines I want to thank the in vitro\r\ncrew of the lab, Jörg, Anne and Alex, for lots of ideas and productive\r\ndiscussions. I am sure, some day we will reveal the secret of the ‘splodge’.\r\nI want to thank the members of the Heisenberg Lab for a great time and\r\nthrilling kicker matches. In this regard I especially want to thank Maurizio\r\n‘Gnocci’ Monti, Gabriel Krens, Alex Eichner, Martin Behrndt, Vanessa Barone,Philipp Schmalhorst, Michael Smutny, Daniel Capek, Anne Reversat, Eva\r\nKiermaier, Frank Assen and Jan Müller for wonderful after-lunch matches.\r\nI would not have been able to analyze the thousands of cell trajectories\r\nand probably hundreds of thousands of mouse clicks without the productive\r\ncollaboration with Veronika Bierbaum and Tobias Bollenbach. Thanks Vroni for\r\ncountless meetings, discussions and graphs and of course for proofreading and\r\nadvice for this thesis. For proofreading I also want to thank Evi, Jörg, Jack and\r\nAnne.\r\nI would like to acknowledge Matthias Mehling for a very productive\r\ncollaboration and for introducing me into the wild world of microfluidics. Jack\r\nMerrin, for countless wafers, PDMS coated coverslips and help with anything\r\nmicro-fabrication related. And Maria Nemethova for establishing the ‘click’\r\npatterning approach with me. Without her it still would be just one of the ideas…\r\nMany thanks to Ekaterina Papusheva, Robert Hauschild, Doreen Milius\r\nand Nasser Darwish from the Bioimaging Facility as well as the Preclinical and\r\nthe Life Science facilities of IST Austria for excellent technical support. At this\r\npoint I especially want to thank Robert for countless image analyses and\r\ntechnical ideas. Always interested and creative he played an essential role in all\r\nof my projects.\r\nAdditionally I want to thank Ingrid and Gabby for welcoming me warmly\r\nwhen I first started at IST, for scientific and especially mental support in all\r\nthose years, countless coffee sessions and Heurigen evenings. #BioimagingFacility #LifeScienceFacility #PreClinicalFacility","file_date_updated":"2021-02-22T11:43:14Z","file":[{"creator":"dernst","content_type":"application/pdf","file_name":"Thesis_JSchwarz_final.pdf","checksum":"e3cd6b28f9c5cccb8891855565a2dade","relation":"main_file","file_id":"6813","date_updated":"2019-08-13T10:55:35Z","access_level":"closed","file_size":32044069,"date_created":"2019-08-13T10:55:35Z"},{"date_updated":"2021-02-22T11:43:14Z","access_level":"open_access","file_size":8396717,"date_created":"2021-02-22T11:43:14Z","success":1,"creator":"dernst","checksum":"c3dbe219acf87eed2f46d21d5cca00de","content_type":"application/pdf","file_name":"2016_Thesis_JSchwarz.pdf","relation":"main_file","file_id":"9181"}],"status":"public","article_processing_charge":"No","_id":"1129","author":[{"last_name":"Schwarz","full_name":"Schwarz, Jan","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"day":"01","year":"2016","date_published":"2016-07-01T00:00:00Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","department":[{"_id":"MiSi"}]},{"file":[{"access_level":"open_access","date_updated":"2020-07-14T12:44:43Z","date_created":"2020-05-14T16:33:46Z","file_size":4433280,"file_name":"2018_NatureCell_Leithner.pdf","checksum":"e1411cb7c99a2d9089c178a6abef25e7","content_type":"application/pdf","creator":"dernst","file_id":"7844","relation":"main_file"}],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","status":"public","ec_funded":1,"file_date_updated":"2020-07-14T12:44:43Z","volume":18,"acknowledgement":"This work was supported by the German Research Foundation (DFG) Priority Program SP 1464 to T.E.B.S. and M.S., and European Research Council (ERC GA 281556) and Human Frontiers Program grants to M.S.\r\nService Units of IST Austria for excellent technical support.","publist_id":"5949","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","day":"24","year":"2016","date_published":"2016-10-24T00:00:00Z","publisher":"Nature Publishing Group","article_processing_charge":"No","_id":"1321","author":[{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","last_name":"Leithner"},{"last_name":"Eichner","full_name":"Eichner, Alexander","id":"4DFA52AE-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander"},{"last_name":"Müller","full_name":"Müller, Jan","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D","first_name":"Jan"},{"first_name":"Anne","id":"35B76592-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0666-8928","full_name":"Reversat, Anne","last_name":"Reversat"},{"last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus"},{"last_name":"Schwarz","full_name":"Schwarz, Jan","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","last_name":"Merrin"},{"first_name":"David","last_name":"De Gorter","full_name":"De Gorter, David"},{"full_name":"Schur, Florian","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0003-4790-8078"},{"last_name":"Bayerl","full_name":"Bayerl, Jonathan","first_name":"Jonathan"},{"last_name":"De Vries","full_name":"De Vries, Ingrid","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-2670-2217","first_name":"Stefan","id":"355AA5A0-F248-11E8-B48F-1D18A9856A87","last_name":"Wieser","full_name":"Wieser, Stefan"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Lai","full_name":"Lai, Frank","first_name":"Frank"},{"last_name":"Moser","full_name":"Moser, Markus","first_name":"Markus"},{"first_name":"Dontscho","last_name":"Kerjaschki","full_name":"Kerjaschki, Dontscho"},{"first_name":"Klemens","full_name":"Rottner, Klemens","last_name":"Rottner"},{"full_name":"Small, Victor","last_name":"Small","first_name":"Victor"},{"first_name":"Theresia","full_name":"Stradal, Theresia","last_name":"Stradal"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K"}],"citation":{"mla":"Leithner, Alexander F., et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature Cell Biology, vol. 18, Nature Publishing Group, 2016, pp. 1253–59, doi:10.1038/ncb3426.","short":"A.F. Leithner, A. Eichner, J. Müller, A. Reversat, M. Brown, J. Schwarz, J. Merrin, D. De Gorter, F.K. Schur, J. Bayerl, I. de Vries, S. Wieser, R. Hauschild, F. Lai, M. Moser, D. Kerjaschki, K. Rottner, V. Small, T. Stradal, M.K. Sixt, Nature Cell Biology 18 (2016) 1253–1259.","chicago":"Leithner, Alexander F, Alexander Eichner, Jan Müller, Anne Reversat, Markus Brown, Jan Schwarz, Jack Merrin, et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature Cell Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/ncb3426.","apa":"Leithner, A. F., Eichner, A., Müller, J., Reversat, A., Brown, M., Schwarz, J., … Sixt, M. K. (2016). Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. Nature Publishing Group. https://doi.org/10.1038/ncb3426","ieee":"A. F. Leithner et al., “Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes,” Nature Cell Biology, vol. 18. Nature Publishing Group, pp. 1253–1259, 2016.","ama":"Leithner AF, Eichner A, Müller J, et al. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. 2016;18:1253-1259. doi:10.1038/ncb3426","ista":"Leithner AF, Eichner A, Müller J, Reversat A, Brown M, Schwarz J, Merrin J, De Gorter D, Schur FK, Bayerl J, de Vries I, Wieser S, Hauschild R, Lai F, Moser M, Kerjaschki D, Rottner K, Small V, Stradal T, Sixt MK. 2016. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. 18, 1253–1259."},"article_type":"original","tmp":{"short":"CC BY-NC-SA (4.0)","image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"type":"journal_article","quality_controlled":"1","project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556"}],"has_accepted_license":"1","related_material":{"record":[{"id":"323","relation":"dissertation_contains","status":"public"}]},"title":"Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes","acknowledged_ssus":[{"_id":"SSU"}],"abstract":[{"lang":"eng","text":"Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion."}],"external_id":{"isi":["000387165600018"]},"doi":"10.1038/ncb3426","oa_version":"Submitted Version","language":[{"iso":"eng"}],"scopus_import":"1","publication_status":"published","date_updated":"2026-06-05T22:30:56Z","intvolume":" 18","oa":1,"publication":"Nature Cell Biology","page":"1253 - 1259","date_created":"2018-12-11T11:51:21Z","ddc":["570"],"isi":1,"month":"10","corr_author":"1"},{"publist_id":"5641","status":"public","volume":12,"publisher":"IOP Publishing","_id":"1530","article_processing_charge":"No","author":[{"first_name":"Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87","full_name":"Bierbaum, Veronika","last_name":"Bierbaum"},{"full_name":"Klumpp, Stefan","last_name":"Klumpp","first_name":"Stefan"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"date_published":"2015-09-25T00:00:00Z","day":"25","year":"2015","quality_controlled":"1","type":"journal_article","citation":{"mla":"Bierbaum, Veronika, and Stefan Klumpp. “Impact of the Cell Division Cycle on Gene Circuits.” Physical Biology, vol. 12, no. 6, 066003, IOP Publishing, 2015, doi:10.1088/1478-3975/12/6/066003.","ama":"Bierbaum V, Klumpp S. Impact of the cell division cycle on gene circuits. Physical Biology. 2015;12(6). doi:10.1088/1478-3975/12/6/066003","ista":"Bierbaum V, Klumpp S. 2015. Impact of the cell division cycle on gene circuits. Physical Biology. 12(6), 066003.","short":"V. Bierbaum, S. Klumpp, Physical Biology 12 (2015).","chicago":"Bierbaum, Veronika, and Stefan Klumpp. “Impact of the Cell Division Cycle on Gene Circuits.” Physical Biology. IOP Publishing, 2015. https://doi.org/10.1088/1478-3975/12/6/066003.","ieee":"V. Bierbaum and S. Klumpp, “Impact of the cell division cycle on gene circuits,” Physical Biology, vol. 12, no. 6. IOP Publishing, 2015.","apa":"Bierbaum, V., & Klumpp, S. (2015). Impact of the cell division cycle on gene circuits. Physical Biology. IOP Publishing. https://doi.org/10.1088/1478-3975/12/6/066003"},"article_number":"066003","issue":"6","doi":"10.1088/1478-3975/12/6/066003","abstract":[{"text":"In growing cells, protein synthesis and cell growth are typically not synchronous, and, thus, protein concentrations vary over the cell division cycle. We have developed a theoretical description of genetic regulatory systems in bacteria that explicitly considers the cell division cycle to investigate its impact on gene expression. We calculate the cell-to-cell variations arising from cells being at different stages in the division cycle for unregulated genes and for basic regulatory mechanisms. These variations contribute to the extrinsic noise observed in single-cell experiments, and are most significant for proteins with short lifetimes. Negative autoregulation buffers against variation of protein concentration over the division cycle, but the effect is found to be relatively weak. Stronger buffering is achieved by an increased protein lifetime. Positive autoregulation can strongly amplify such variation if the parameters are set to values that lead to resonance-like behaviour. For cooperative positive autoregulation, the concentration variation over the division cycle diminishes the parameter region of bistability and modulates the switching times between the two stable states. The same effects are seen for a two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit, the repressilator, is only weakly affected by the division cycle.","lang":"eng"}],"title":"Impact of the cell division cycle on gene circuits","external_id":{"isi":["000368186300009"]},"scopus_import":"1","date_updated":"2025-09-23T09:19:53Z","publication_status":"published","language":[{"iso":"eng"}],"oa_version":"None","intvolume":" 12","month":"09","isi":1,"corr_author":"1","date_created":"2018-12-11T11:52:33Z","publication":"Physical Biology"},{"corr_author":"1","month":"04","isi":1,"date_created":"2018-12-11T11:52:41Z","page":"374 - 386","publication":"Cell","intvolume":" 161","date_updated":"2025-09-23T07:31:01Z","publication_status":"published","scopus_import":"1","language":[{"iso":"eng"}],"oa_version":"None","doi":"10.1016/j.cell.2015.01.056","external_id":{"isi":["000352708300028"]},"title":"Actin flows mediate a universal coupling between cell speed and cell persistence","abstract":[{"lang":"eng","text":"Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns."}],"issue":"2","quality_controlled":"1","project":[{"call_identifier":"FWF","_id":"2529486C-B435-11E9-9278-68D0E5697425","name":"Cell- and Tissue Mechanics in Zebrafish Germ Layer Formation","grant_number":"T 560-B17"},{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7","grant_number":"281556"},{"grant_number":"RGP0058/2011","_id":"25ABD200-B435-11E9-9278-68D0E5697425","name":"Cell migration in complex environments: from in vivo experiments to theoretical models"}],"type":"journal_article","citation":{"mla":"Maiuri, Paolo, et al. “Actin Flows Mediate a Universal Coupling between Cell Speed and Cell Persistence.” Cell, vol. 161, no. 2, Cell Press, 2015, pp. 374–86, doi:10.1016/j.cell.2015.01.056.","short":"P. Maiuri, J. Rupprecht, S. Wieser, V. Ruprecht, O. Bénichou, N. Carpi, M. Coppey, S. De Beco, N. Gov, C.-P.J. Heisenberg, C. Lage Crespo, F. Lautenschlaeger, M. Le Berre, A. Lennon Duménil, M. Raab, H. Thiam, M. Piel, M.K. Sixt, R. Voituriez, Cell 161 (2015) 374–386.","chicago":"Maiuri, Paolo, Jean Rupprecht, Stefan Wieser, Verena Ruprecht, Olivier Bénichou, Nicolas Carpi, Mathieu Coppey, et al. “Actin Flows Mediate a Universal Coupling between Cell Speed and Cell Persistence.” Cell. Cell Press, 2015. https://doi.org/10.1016/j.cell.2015.01.056.","ieee":"P. Maiuri et al., “Actin flows mediate a universal coupling between cell speed and cell persistence,” Cell, vol. 161, no. 2. Cell Press, pp. 374–386, 2015.","apa":"Maiuri, P., Rupprecht, J., Wieser, S., Ruprecht, V., Bénichou, O., Carpi, N., … Voituriez, R. (2015). Actin flows mediate a universal coupling between cell speed and cell persistence. Cell. Cell Press. https://doi.org/10.1016/j.cell.2015.01.056","ista":"Maiuri P, Rupprecht J, Wieser S, Ruprecht V, Bénichou O, Carpi N, Coppey M, De Beco S, Gov N, Heisenberg C-PJ, Lage Crespo C, Lautenschlaeger F, Le Berre M, Lennon Duménil A, Raab M, Thiam H, Piel M, Sixt MK, Voituriez R. 2015. Actin flows mediate a universal coupling between cell speed and cell persistence. Cell. 161(2), 374–386.","ama":"Maiuri P, Rupprecht J, Wieser S, et al. Actin flows mediate a universal coupling between cell speed and cell persistence. Cell. 2015;161(2):374-386. doi:10.1016/j.cell.2015.01.056"},"article_processing_charge":"No","_id":"1553","author":[{"first_name":"Paolo","full_name":"Maiuri, Paolo","last_name":"Maiuri"},{"last_name":"Rupprecht","full_name":"Rupprecht, Jean","first_name":"Jean"},{"id":"355AA5A0-F248-11E8-B48F-1D18A9856A87","first_name":"Stefan","orcid":"0000-0002-2670-2217","full_name":"Wieser, Stefan","last_name":"Wieser"},{"full_name":"Ruprecht, Verena","last_name":"Ruprecht","first_name":"Verena","id":"4D71A03A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4088-8633"},{"full_name":"Bénichou, Olivier","last_name":"Bénichou","first_name":"Olivier"},{"full_name":"Carpi, Nicolas","last_name":"Carpi","first_name":"Nicolas"},{"full_name":"Coppey, Mathieu","last_name":"Coppey","first_name":"Mathieu"},{"first_name":"Simon","full_name":"De Beco, Simon","last_name":"De Beco"},{"first_name":"Nir","full_name":"Gov, Nir","last_name":"Gov"},{"orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J"},{"first_name":"Carolina","last_name":"Lage Crespo","full_name":"Lage Crespo, Carolina"},{"first_name":"Franziska","full_name":"Lautenschlaeger, Franziska","last_name":"Lautenschlaeger"},{"first_name":"Maël","full_name":"Le Berre, Maël","last_name":"Le Berre"},{"first_name":"Ana","full_name":"Lennon Duménil, Ana","last_name":"Lennon Duménil"},{"full_name":"Raab, Matthew","last_name":"Raab","first_name":"Matthew"},{"full_name":"Thiam, Hawa","last_name":"Thiam","first_name":"Hawa"},{"first_name":"Matthieu","full_name":"Piel, Matthieu","last_name":"Piel"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"},{"last_name":"Voituriez","full_name":"Voituriez, Raphaël","first_name":"Raphaël"}],"publisher":"Cell Press","date_published":"2015-04-09T00:00:00Z","year":"2015","day":"09","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"},{"_id":"CaHe"}],"publist_id":"5618","volume":161,"ec_funded":1,"status":"public"},{"publication_status":"published","date_updated":"2025-09-23T14:03:22Z","scopus_import":"1","language":[{"iso":"eng"}],"oa_version":"None","doi":"10.1038/ni.3126","external_id":{"isi":["000351333700005"]},"abstract":[{"lang":"eng","text":"Stromal cells in the subcapsular sinus of the lymph node 'decide' which cells and molecules are allowed access to the deeper parenchyma. The glycoprotein PLVAP is a crucial component of this selector function."}],"title":"The lymph node filter revealed","corr_author":"1","month":"03","isi":1,"date_created":"2018-12-11T11:52:43Z","publication":"Nature Immunology","page":"338 - 340","intvolume":" 16","_id":"1560","author":[{"full_name":"Hons, Miroslav","last_name":"Hons","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","first_name":"Miroslav","orcid":"0000-0002-6625-3348"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"article_processing_charge":"No","publisher":"Nature Publishing Group","date_published":"2015-03-19T00:00:00Z","year":"2015","day":"19","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"publist_id":"5611","volume":16,"status":"public","issue":"4","quality_controlled":"1","type":"journal_article","citation":{"short":"M. Hons, M.K. Sixt, Nature Immunology 16 (2015) 338–340.","chicago":"Hons, Miroslav, and Michael K Sixt. “The Lymph Node Filter Revealed.” Nature Immunology. Nature Publishing Group, 2015. https://doi.org/10.1038/ni.3126.","apa":"Hons, M., & Sixt, M. K. (2015). The lymph node filter revealed. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3126","ieee":"M. Hons and M. K. Sixt, “The lymph node filter revealed,” Nature Immunology, vol. 16, no. 4. Nature Publishing Group, pp. 338–340, 2015.","ista":"Hons M, Sixt MK. 2015. The lymph node filter revealed. Nature Immunology. 16(4), 338–340.","ama":"Hons M, Sixt MK. The lymph node filter revealed. Nature Immunology. 2015;16(4):338-340. doi:10.1038/ni.3126","mla":"Hons, Miroslav, and Michael K. Sixt. “The Lymph Node Filter Revealed.” Nature Immunology, vol. 16, no. 4, Nature Publishing Group, 2015, pp. 338–40, doi:10.1038/ni.3126."}},{"publication_status":"published","date_updated":"2025-09-22T14:33:46Z","scopus_import":"1","oa_version":"None","language":[{"iso":"eng"}],"doi":"10.1002/eji.201545457","external_id":{"isi":["000355836500006"]},"abstract":[{"lang":"eng","text":"Replication-deficient recombinant adenoviruses are potent vectors for the efficient transient expression of exogenous genes in resting immune cells. However, most leukocytes are refractory to efficient adenoviral transduction as they lack expression of the coxsackie/adenovirus receptor (CAR). To circumvent this obstacle, we generated the R26/CAG-CARΔ1StopF (where R26 is ROSA26 and CAG is CMV early enhancer/chicken β actin promoter) knock-in mouse line. This strain allows monitoring of in situ Cre recombinase activity through expression of CARΔ1. Simultaneously, CARΔ1 expression permits selective and highly efficient adenoviral transduction of immune cell populations, such as mast cells or T cells, directly ex vivo in bulk cultures without prior cell purification or activation. Furthermore, we show that CARΔ1 expression dramatically improves adenoviral infection of in vitro differentiated conventional and plasmacytoid dendritic cells (DCs), basophils, mast cells, as well as Hoxb8-immortalized hematopoietic progenitor cells. This novel dual function mouse strain will hence be a valuable tool to rapidly dissect the function of specific genes in leukocyte physiology."}],"title":"A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors","isi":1,"month":"06","publication":"European Journal of Immunology","page":"1614 - 1620","date_created":"2018-12-11T11:52:44Z","intvolume":" 45","_id":"1561","author":[{"full_name":"Heger, Klaus","last_name":"Heger","first_name":"Klaus"},{"full_name":"Kober, Maike","last_name":"Kober","first_name":"Maike"},{"first_name":"David","full_name":"Rieß, David","last_name":"Rieß"},{"last_name":"Drees","full_name":"Drees, Christoph","first_name":"Christoph"},{"first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","full_name":"De Vries, Ingrid"},{"full_name":"Bertossi, Arianna","last_name":"Bertossi","first_name":"Arianna"},{"last_name":"Roers","full_name":"Roers, Axel","first_name":"Axel"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"},{"full_name":"Schmidt Supprian, Marc","last_name":"Schmidt Supprian","first_name":"Marc"}],"article_processing_charge":"No","publisher":"Wiley","day":"01","year":"2015","date_published":"2015-06-01T00:00:00Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"publist_id":"5610","volume":45,"status":"public","issue":"6","type":"journal_article","quality_controlled":"1","citation":{"ama":"Heger K, Kober M, Rieß D, et al. A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors. European Journal of Immunology. 2015;45(6):1614-1620. doi:10.1002/eji.201545457","ista":"Heger K, Kober M, Rieß D, Drees C, de Vries I, Bertossi A, Roers A, Sixt MK, Schmidt Supprian M. 2015. A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors. European Journal of Immunology. 45(6), 1614–1620.","apa":"Heger, K., Kober, M., Rieß, D., Drees, C., de Vries, I., Bertossi, A., … Schmidt Supprian, M. (2015). A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors. European Journal of Immunology. Wiley. https://doi.org/10.1002/eji.201545457","ieee":"K. Heger et al., “A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors,” European Journal of Immunology, vol. 45, no. 6. Wiley, pp. 1614–1620, 2015.","short":"K. Heger, M. Kober, D. Rieß, C. Drees, I. de Vries, A. Bertossi, A. Roers, M.K. Sixt, M. Schmidt Supprian, European Journal of Immunology 45 (2015) 1614–1620.","chicago":"Heger, Klaus, Maike Kober, David Rieß, Christoph Drees, Ingrid de Vries, Arianna Bertossi, Axel Roers, Michael K Sixt, and Marc Schmidt Supprian. “A Novel Cre Recombinase Reporter Mouse Strain Facilitates Selective and Efficient Infection of Primary Immune Cells with Adenoviral Vectors.” European Journal of Immunology. Wiley, 2015. https://doi.org/10.1002/eji.201545457.","mla":"Heger, Klaus, et al. “A Novel Cre Recombinase Reporter Mouse Strain Facilitates Selective and Efficient Infection of Primary Immune Cells with Adenoviral Vectors.” European Journal of Immunology, vol. 45, no. 6, Wiley, 2015, pp. 1614–20, doi:10.1002/eji.201545457."}},{"month":"06","isi":1,"ddc":["570"],"date_created":"2018-12-11T11:52:48Z","publication":"Nature Communications","oa":1,"intvolume":" 6","scopus_import":"1","publication_status":"published","date_updated":"2025-09-23T08:13:23Z","language":[{"iso":"eng"}],"oa_version":"Published Version","doi":"10.1038/ncomms8526","title":"Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells","abstract":[{"lang":"eng","text":"The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space."}],"external_id":{"isi":["000357179400003"]},"article_number":"7526","has_accepted_license":"1","quality_controlled":"1","type":"journal_article","citation":{"mla":"Chabaud, Mélanie, et al. “Cell Migration and Antigen Capture Are Antagonistic Processes Coupled by Myosin II in Dendritic Cells.” Nature Communications, vol. 6, 7526, Nature Publishing Group, 2015, doi:10.1038/ncomms8526.","ista":"Chabaud M, Heuzé M, Bretou M, Vargas P, Maiuri P, Solanes P, Maurin M, Terriac E, Le Berre M, Lankar D, Piolot T, Adelstein R, Zhang Y, Sixt MK, Jacobelli J, Bénichou O, Voituriez R, Piel M, Lennon Duménil A. 2015. Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells. Nature Communications. 6, 7526.","ama":"Chabaud M, Heuzé M, Bretou M, et al. Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells. Nature Communications. 2015;6. doi:10.1038/ncomms8526","chicago":"Chabaud, Mélanie, Mélina Heuzé, Marine Bretou, Pablo Vargas, Paolo Maiuri, Paola Solanes, Mathieu Maurin, et al. “Cell Migration and Antigen Capture Are Antagonistic Processes Coupled by Myosin II in Dendritic Cells.” Nature Communications. Nature Publishing Group, 2015. https://doi.org/10.1038/ncomms8526.","short":"M. Chabaud, M. Heuzé, M. Bretou, P. Vargas, P. Maiuri, P. Solanes, M. Maurin, E. Terriac, M. Le Berre, D. Lankar, T. Piolot, R. Adelstein, Y. Zhang, M.K. Sixt, J. Jacobelli, O. Bénichou, R. Voituriez, M. Piel, A. Lennon Duménil, Nature Communications 6 (2015).","ieee":"M. Chabaud et al., “Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells,” Nature Communications, vol. 6. Nature Publishing Group, 2015.","apa":"Chabaud, M., Heuzé, M., Bretou, M., Vargas, P., Maiuri, P., Solanes, P., … Lennon Duménil, A. (2015). Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms8526"},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publisher":"Nature Publishing Group","_id":"1575","article_processing_charge":"No","author":[{"first_name":"Mélanie","full_name":"Chabaud, Mélanie","last_name":"Chabaud"},{"first_name":"Mélina","full_name":"Heuzé, Mélina","last_name":"Heuzé"},{"last_name":"Bretou","full_name":"Bretou, Marine","first_name":"Marine"},{"first_name":"Pablo","last_name":"Vargas","full_name":"Vargas, Pablo"},{"last_name":"Maiuri","full_name":"Maiuri, Paolo","first_name":"Paolo"},{"first_name":"Paola","full_name":"Solanes, Paola","last_name":"Solanes"},{"last_name":"Maurin","full_name":"Maurin, Mathieu","first_name":"Mathieu"},{"full_name":"Terriac, Emmanuel","last_name":"Terriac","first_name":"Emmanuel"},{"full_name":"Le Berre, Maël","last_name":"Le Berre","first_name":"Maël"},{"first_name":"Danielle","full_name":"Lankar, Danielle","last_name":"Lankar"},{"full_name":"Piolot, Tristan","last_name":"Piolot","first_name":"Tristan"},{"first_name":"Robert","full_name":"Adelstein, Robert","last_name":"Adelstein"},{"first_name":"Yingfan","full_name":"Zhang, Yingfan","last_name":"Zhang"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"},{"first_name":"Jordan","full_name":"Jacobelli, Jordan","last_name":"Jacobelli"},{"full_name":"Bénichou, Olivier","last_name":"Bénichou","first_name":"Olivier"},{"first_name":"Raphaël","last_name":"Voituriez","full_name":"Voituriez, Raphaël"},{"first_name":"Matthieu","last_name":"Piel","full_name":"Piel, Matthieu"},{"full_name":"Lennon Duménil, Ana","last_name":"Lennon Duménil","first_name":"Ana"}],"department":[{"_id":"MiSi"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2015-06-25T00:00:00Z","pubrep_id":"476","year":"2015","day":"25","acknowledgement":"M.C. and M.L.H. were supported by fellowships from the Fondation pour la Recherche Médicale and the Association pour la Recherche contre le Cancer, respectively. This work was funded by grants from the City of Paris and the European Research Council to A.-M.L.-D. (Strapacemi 243103), the Association Nationale pour la Recherche (ANR-09-PIRI-0027-PCVI) and the InnaBiosanté foundation (Micemico) to A.-M.L.-D., M.P. and R.V., and the DCBIOL Labex from the French Government (ANR-10-IDEX-0001-02-PSL* and ANR-11-LABX-0043). The super-resolution SIM microscope was funded through an ERC Advanced Investigator Grant (250367) to Edith Heard (CNRS UMR3215/Inserm U934, Institut Curie).","publist_id":"5596","status":"public","file":[{"date_updated":"2020-07-14T12:45:02Z","access_level":"open_access","file_size":4530215,"date_created":"2018-12-12T10:11:58Z","creator":"system","file_name":"IST-2016-476-v1+1_ncomms8526.pdf","content_type":"application/pdf","checksum":"bae12e86be2adb28253f890b8bba8315","relation":"main_file","file_id":"4915"}],"license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2020-07-14T12:45:02Z","volume":6},{"ec_funded":1,"status":"public","volume":54,"publist_id":"5548","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"year":"2015","day":"26","date_published":"2015-06-26T00:00:00Z","publisher":"American Chemical Society","author":[{"first_name":"Christopher","last_name":"Veldkamp","full_name":"Veldkamp, Christopher"},{"last_name":"Kiermaier","full_name":"Kiermaier, Eva","orcid":"0000-0001-6165-5738","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","first_name":"Eva"},{"first_name":"Skylar","last_name":"Gabel Eissens","full_name":"Gabel Eissens, Skylar"},{"first_name":"Miranda","full_name":"Gillitzer, Miranda","last_name":"Gillitzer"},{"first_name":"David","last_name":"Lippner","full_name":"Lippner, David"},{"last_name":"Disilvio","full_name":"Disilvio, Frank","first_name":"Frank"},{"last_name":"Mueller","full_name":"Mueller, Casey","first_name":"Casey"},{"full_name":"Wantuch, Paeton","last_name":"Wantuch","first_name":"Paeton"},{"first_name":"Gary","full_name":"Chaffee, Gary","last_name":"Chaffee"},{"last_name":"Famiglietti","full_name":"Famiglietti, Michael","first_name":"Michael"},{"first_name":"Danielle","full_name":"Zgoba, Danielle","last_name":"Zgoba"},{"last_name":"Bailey","full_name":"Bailey, Asha","first_name":"Asha"},{"first_name":"Yaya","last_name":"Bah","full_name":"Bah, Yaya"},{"full_name":"Engebretson, Samantha","last_name":"Engebretson","first_name":"Samantha"},{"first_name":"David","full_name":"Graupner, David","last_name":"Graupner"},{"first_name":"Emily","full_name":"Lackner, Emily","last_name":"Lackner"},{"first_name":"Vincent","full_name":"Larosa, Vincent","last_name":"Larosa"},{"first_name":"Tysha","full_name":"Medeiros, Tysha","last_name":"Medeiros"},{"full_name":"Olson, Michael","last_name":"Olson","first_name":"Michael"},{"first_name":"Andrew","full_name":"Phillips, Andrew","last_name":"Phillips"},{"first_name":"Harley","full_name":"Pyles, Harley","last_name":"Pyles"},{"full_name":"Richard, Amanda","last_name":"Richard","first_name":"Amanda"},{"full_name":"Schoeller, Scott","last_name":"Schoeller","first_name":"Scott"},{"first_name":"Boris","full_name":"Touzeau, Boris","last_name":"Touzeau"},{"first_name":"Larry","last_name":"Williams","full_name":"Williams, Larry"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"},{"full_name":"Peterson, Francis","last_name":"Peterson","first_name":"Francis"}],"_id":"1618","article_processing_charge":"No","citation":{"ieee":"C. Veldkamp et al., “Solution structure of CCL19 and identification of overlapping CCR7 and PSGL-1 binding sites,” Biochemistry, vol. 54, no. 27. American Chemical Society, pp. 4163–4166, 2015.","apa":"Veldkamp, C., Kiermaier, E., Gabel Eissens, S., Gillitzer, M., Lippner, D., Disilvio, F., … Peterson, F. (2015). Solution structure of CCL19 and identification of overlapping CCR7 and PSGL-1 binding sites. Biochemistry. American Chemical Society. https://doi.org/10.1021/acs.biochem.5b00560","chicago":"Veldkamp, Christopher, Eva Kiermaier, Skylar Gabel Eissens, Miranda Gillitzer, David Lippner, Frank Disilvio, Casey Mueller, et al. “Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL-1 Binding Sites.” Biochemistry. American Chemical Society, 2015. https://doi.org/10.1021/acs.biochem.5b00560.","short":"C. Veldkamp, E. Kiermaier, S. Gabel Eissens, M. Gillitzer, D. Lippner, F. Disilvio, C. Mueller, P. Wantuch, G. Chaffee, M. Famiglietti, D. Zgoba, A. Bailey, Y. Bah, S. Engebretson, D. Graupner, E. Lackner, V. Larosa, T. Medeiros, M. Olson, A. Phillips, H. Pyles, A. Richard, S. Schoeller, B. Touzeau, L. Williams, M.K. Sixt, F. Peterson, Biochemistry 54 (2015) 4163–4166.","ista":"Veldkamp C, Kiermaier E, Gabel Eissens S, Gillitzer M, Lippner D, Disilvio F, Mueller C, Wantuch P, Chaffee G, Famiglietti M, Zgoba D, Bailey A, Bah Y, Engebretson S, Graupner D, Lackner E, Larosa V, Medeiros T, Olson M, Phillips A, Pyles H, Richard A, Schoeller S, Touzeau B, Williams L, Sixt MK, Peterson F. 2015. Solution structure of CCL19 and identification of overlapping CCR7 and PSGL-1 binding sites. Biochemistry. 54(27), 4163–4166.","ama":"Veldkamp C, Kiermaier E, Gabel Eissens S, et al. Solution structure of CCL19 and identification of overlapping CCR7 and PSGL-1 binding sites. Biochemistry. 2015;54(27):4163-4166. doi:10.1021/acs.biochem.5b00560","mla":"Veldkamp, Christopher, et al. “Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL-1 Binding Sites.” Biochemistry, vol. 54, no. 27, American Chemical Society, 2015, pp. 4163–66, doi:10.1021/acs.biochem.5b00560."},"type":"journal_article","quality_controlled":"1","project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556"}],"pmid":1,"issue":"27","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809050/","open_access":"1"}],"abstract":[{"lang":"eng","text":"CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1's enhancement of resting T-cell recruitment are discussed."}],"title":"Solution structure of CCL19 and identification of overlapping CCR7 and PSGL-1 binding sites","external_id":{"pmid":["26115234"],"isi":["000358105100001"]},"doi":"10.1021/acs.biochem.5b00560","oa_version":"Submitted Version","language":[{"iso":"eng"}],"scopus_import":"1","publication_status":"published","date_updated":"2025-09-23T10:47:25Z","intvolume":" 54","oa":1,"publication":"Biochemistry","page":"4163 - 4166","date_created":"2018-12-11T11:53:03Z","isi":1,"month":"06"},{"external_id":{"isi":["000364577600001"]},"volume":36,"status":"public","title":"Editorial overview: Cell adhesion and migration","publist_id":"5473","doi":"10.1016/j.ceb.2015.09.004","oa_version":"None","year":"2015","day":"01","language":[{"iso":"eng"}],"date_published":"2015-10-01T00:00:00Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"_id":"1676","author":[{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"},{"full_name":"Raz, Erez","last_name":"Raz","first_name":"Erez"}],"article_processing_charge":"No","date_updated":"2025-09-23T08:35:11Z","publication_status":"published","publisher":"Elsevier","scopus_import":"1","citation":{"mla":"Sixt, Michael K., and Erez Raz. “Editorial Overview: Cell Adhesion and Migration.” Current Opinion in Cell Biology, vol. 36, no. 10, Elsevier, 2015, pp. 4–6, doi:10.1016/j.ceb.2015.09.004.","short":"M.K. Sixt, E. Raz, Current Opinion in Cell Biology 36 (2015) 4–6.","chicago":"Sixt, Michael K, and Erez Raz. “Editorial Overview: Cell Adhesion and Migration.” Current Opinion in Cell Biology. Elsevier, 2015. https://doi.org/10.1016/j.ceb.2015.09.004.","ieee":"M. K. Sixt and E. Raz, “Editorial overview: Cell adhesion and migration,” Current Opinion in Cell Biology, vol. 36, no. 10. Elsevier, pp. 4–6, 2015.","apa":"Sixt, M. K., & Raz, E. (2015). Editorial overview: Cell adhesion and migration. Current Opinion in Cell Biology. Elsevier. https://doi.org/10.1016/j.ceb.2015.09.004","ama":"Sixt MK, Raz E. Editorial overview: Cell adhesion and migration. Current Opinion in Cell Biology. 2015;36(10):4-6. doi:10.1016/j.ceb.2015.09.004","ista":"Sixt MK, Raz E. 2015. Editorial overview: Cell adhesion and migration. Current Opinion in Cell Biology. 36(10), 4–6."},"intvolume":" 36","type":"journal_article","page":"4 - 6","publication":"Current Opinion in Cell Biology","date_created":"2018-12-11T11:53:25Z","isi":1,"issue":"10","month":"10"},{"month":"09","isi":1,"corr_author":"1","date_created":"2018-12-11T11:53:28Z","publication":"Science","page":"1055 - 1056","intvolume":" 349","scopus_import":"1","publication_status":"published","date_updated":"2025-09-23T08:52:36Z","language":[{"iso":"eng"}],"oa_version":"None","doi":"10.1126/science.aad0867","title":"Fragmented communication between immune cells: Neutrophils blaze a trail with migratory cues for T cells to follow to sites of infection","external_id":{"isi":["000360628900020"]},"issue":"6252","quality_controlled":"1","type":"journal_article","citation":{"mla":"Kiermaier, Eva, and Michael K. Sixt. “Fragmented Communication between Immune Cells: Neutrophils Blaze a Trail with Migratory Cues for T Cells to Follow to Sites of Infection.” Science, vol. 349, no. 6252, American Association for the Advancement of Science, 2015, pp. 1055–56, doi:10.1126/science.aad0867.","ama":"Kiermaier E, Sixt MK. Fragmented communication between immune cells: Neutrophils blaze a trail with migratory cues for T cells to follow to sites of infection. Science. 2015;349(6252):1055-1056. doi:10.1126/science.aad0867","ista":"Kiermaier E, Sixt MK. 2015. Fragmented communication between immune cells: Neutrophils blaze a trail with migratory cues for T cells to follow to sites of infection. Science. 349(6252), 1055–1056.","apa":"Kiermaier, E., & Sixt, M. K. (2015). Fragmented communication between immune cells: Neutrophils blaze a trail with migratory cues for T cells to follow to sites of infection. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aad0867","ieee":"E. Kiermaier and M. K. Sixt, “Fragmented communication between immune cells: Neutrophils blaze a trail with migratory cues for T cells to follow to sites of infection,” Science, vol. 349, no. 6252. American Association for the Advancement of Science, pp. 1055–1056, 2015.","chicago":"Kiermaier, Eva, and Michael K Sixt. “Fragmented Communication between Immune Cells: Neutrophils Blaze a Trail with Migratory Cues for T Cells to Follow to Sites of Infection.” Science. American Association for the Advancement of Science, 2015. https://doi.org/10.1126/science.aad0867.","short":"E. Kiermaier, M.K. Sixt, Science 349 (2015) 1055–1056."},"publisher":"American Association for the Advancement of Science","_id":"1686","author":[{"orcid":"0000-0001-6165-5738","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","first_name":"Eva","last_name":"Kiermaier","full_name":"Kiermaier, Eva"},{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"article_processing_charge":"No","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"date_published":"2015-09-04T00:00:00Z","year":"2015","day":"04","publist_id":"5459","status":"public","volume":349},{"month":"10","isi":1,"ddc":["570"],"date_created":"2018-12-11T11:53:28Z","publication":"Current Opinion in Cell Biology","page":"93 - 102","oa":1,"intvolume":" 36","scopus_import":"1","date_updated":"2025-09-23T09:39:11Z","publication_status":"published","language":[{"iso":"eng"}],"oa_version":"Published Version","doi":"10.1016/j.ceb.2015.08.001","abstract":[{"text":"Guided cell movement is essential for development and integrity of animals and crucially involved in cellular immune responses. Leukocytes are professional migratory cells that can navigate through most types of tissues and sense a wide range of directional cues. The responses of these cells to attractants have been mainly explored in tissue culture settings. How leukocytes make directional decisions in situ, within the challenging environment of a tissue maze, is less understood. Here we review recent advances in how leukocytes sense chemical cues in complex tissue settings and make links with paradigms of directed migration in development and Dictyostelium discoideum amoebae.","lang":"eng"}],"title":"Navigating in tissue mazes: Chemoattractant interpretation in complex environments","external_id":{"isi":["000364577600014"]},"issue":"10","has_accepted_license":"1","project":[{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"}],"quality_controlled":"1","type":"journal_article","citation":{"ista":"Sarris M, Sixt MK. 2015. Navigating in tissue mazes: Chemoattractant interpretation in complex environments. Current Opinion in Cell Biology. 36(10), 93–102.","ama":"Sarris M, Sixt MK. Navigating in tissue mazes: Chemoattractant interpretation in complex environments. Current Opinion in Cell Biology. 2015;36(10):93-102. doi:10.1016/j.ceb.2015.08.001","apa":"Sarris, M., & Sixt, M. K. (2015). Navigating in tissue mazes: Chemoattractant interpretation in complex environments. Current Opinion in Cell Biology. Elsevier. https://doi.org/10.1016/j.ceb.2015.08.001","ieee":"M. Sarris and M. K. Sixt, “Navigating in tissue mazes: Chemoattractant interpretation in complex environments,” Current Opinion in Cell Biology, vol. 36, no. 10. Elsevier, pp. 93–102, 2015.","chicago":"Sarris, Milka, and Michael K Sixt. “Navigating in Tissue Mazes: Chemoattractant Interpretation in Complex Environments.” Current Opinion in Cell Biology. Elsevier, 2015. https://doi.org/10.1016/j.ceb.2015.08.001.","short":"M. Sarris, M.K. Sixt, Current Opinion in Cell Biology 36 (2015) 93–102.","mla":"Sarris, Milka, and Michael K. Sixt. “Navigating in Tissue Mazes: Chemoattractant Interpretation in Complex Environments.” Current Opinion in Cell Biology, vol. 36, no. 10, Elsevier, 2015, pp. 93–102, doi:10.1016/j.ceb.2015.08.001."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publisher":"Elsevier","author":[{"last_name":"Sarris","full_name":"Sarris, Milka","first_name":"Milka"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K"}],"_id":"1687","article_processing_charge":"No","department":[{"_id":"MiSi"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2015-10-01T00:00:00Z","pubrep_id":"445","day":"01","year":"2015","publist_id":"5458","status":"public","ec_funded":1,"file":[{"date_updated":"2020-07-14T12:45:12Z","access_level":"open_access","file_size":797964,"date_created":"2018-12-12T10:11:21Z","creator":"system","checksum":"c29973924b790aab02fdd91857759cfb","file_name":"IST-2016-445-v1+1_1-s2.0-S0955067415001064-main.pdf","content_type":"application/pdf","relation":"main_file","file_id":"4875"}],"volume":36,"file_date_updated":"2020-07-14T12:45:12Z"},{"quality_controlled":"1","type":"journal_article","citation":{"chicago":"Holst, Katrin, Daria Guseva, Susann Schindler, Michael K Sixt, Armin Braun, Himpriya Chopra, Oliver Pabst, and Evgeni Ponimaskin. “The Serotonin Receptor 5-HT7R Regulates the Morphology and Migratory Properties of Dendritic Cells.” Journal of Cell Science. Company of Biologists, 2015. https://doi.org/10.1242/jcs.167999.","short":"K. Holst, D. Guseva, S. Schindler, M.K. Sixt, A. Braun, H. Chopra, O. Pabst, E. Ponimaskin, Journal of Cell Science 128 (2015) 2866–2880.","ieee":"K. Holst et al., “The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells,” Journal of Cell Science, vol. 128, no. 15. Company of Biologists, pp. 2866–2880, 2015.","apa":"Holst, K., Guseva, D., Schindler, S., Sixt, M. K., Braun, A., Chopra, H., … Ponimaskin, E. (2015). The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells. Journal of Cell Science. Company of Biologists. https://doi.org/10.1242/jcs.167999","ista":"Holst K, Guseva D, Schindler S, Sixt MK, Braun A, Chopra H, Pabst O, Ponimaskin E. 2015. The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells. Journal of Cell Science. 128(15), 2866–2880.","ama":"Holst K, Guseva D, Schindler S, et al. The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells. Journal of Cell Science. 2015;128(15):2866-2880. doi:10.1242/jcs.167999","mla":"Holst, Katrin, et al. “The Serotonin Receptor 5-HT7R Regulates the Morphology and Migratory Properties of Dendritic Cells.” Journal of Cell Science, vol. 128, no. 15, Company of Biologists, 2015, pp. 2866–80, doi:10.1242/jcs.167999."},"issue":"15","publist_id":"7343","volume":128,"status":"public","article_processing_charge":"No","_id":"477","author":[{"first_name":"Katrin","full_name":"Holst, Katrin","last_name":"Holst"},{"last_name":"Guseva","full_name":"Guseva, Daria","first_name":"Daria"},{"first_name":"Susann","full_name":"Schindler, Susann","last_name":"Schindler"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Armin","full_name":"Braun, Armin","last_name":"Braun"},{"first_name":"Himpriya","last_name":"Chopra","full_name":"Chopra, Himpriya"},{"first_name":"Oliver","last_name":"Pabst","full_name":"Pabst, Oliver"},{"last_name":"Ponimaskin","full_name":"Ponimaskin, Evgeni","first_name":"Evgeni"}],"publisher":"Company of Biologists","date_published":"2015-06-15T00:00:00Z","day":"15","year":"2015","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","department":[{"_id":"MiSi"}],"intvolume":" 128","month":"06","isi":1,"date_created":"2018-12-11T11:46:41Z","page":"2866 - 2880","publication":"Journal of Cell Science","doi":"10.1242/jcs.167999","external_id":{"isi":["000359782100013"]},"title":"The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells","abstract":[{"text":"Dendritic cells are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of dendritic cell functions is poorly understood. Here, we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7TR) as well as its downstream effector Cdc42 is upregulated in dendritic cells upon maturation. Although dendritic cell maturation was independent of 5-HT7TR, receptor stimulation affected dendritic cell morphology through Cdc42-mediated signaling. In addition, basal activity of 5-HT7TR was required for the proper expression of the chemokine receptor CCR7, which is a key factor that controls dendritic cell migration. Consistent with this, we observed that 5-HT7TR enhances chemotactic motility of dendritic cells in vitro by modulating their directionality and migration velocity. Accordingly, migration of dendritic cells in murine colon explants was abolished after pharmacological receptor inhibition. Our results indicate that there is a crucial role for 5-HT7TR-Cdc42-mediated signaling in the regulation of dendritic cell morphology and motility, suggesting that 5-HT7TR could be a new target for treatment of a variety of inflammatory and immune disorders.","lang":"eng"}],"date_updated":"2025-09-23T14:16:38Z","publication_status":"published","scopus_import":"1","language":[{"iso":"eng"}],"oa_version":"None"},{"type":"journal_article","project":[{"grant_number":"T 560-B17","call_identifier":"FWF","_id":"2529486C-B435-11E9-9278-68D0E5697425","name":"Cell- and Tissue Mechanics in Zebrafish Germ Layer Formation"},{"grant_number":"I812-B12","call_identifier":"FWF","name":"Cell Cortex and Germ Layer Formation in Zebrafish Gastrulation","_id":"2527D5CC-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","citation":{"ista":"Ruprecht V, Wieser S, Callan Jones A, Smutny M, Morita H, Sako K, Barone V, Ritsch Marte M, Sixt MK, Voituriez R, Heisenberg C-PJ. 2015. Cortical contractility triggers a stochastic switch to fast amoeboid cell motility. Cell. 160(4), 673–685.","ama":"Ruprecht V, Wieser S, Callan Jones A, et al. Cortical contractility triggers a stochastic switch to fast amoeboid cell motility. Cell. 2015;160(4):673-685. doi:10.1016/j.cell.2015.01.008","chicago":"Ruprecht, Verena, Stefan Wieser, Andrew Callan Jones, Michael Smutny, Hitoshi Morita, Keisuke Sako, Vanessa Barone, et al. “Cortical Contractility Triggers a Stochastic Switch to Fast Amoeboid Cell Motility.” Cell. Cell Press, 2015. https://doi.org/10.1016/j.cell.2015.01.008.","short":"V. Ruprecht, S. Wieser, A. Callan Jones, M. Smutny, H. Morita, K. Sako, V. Barone, M. Ritsch Marte, M.K. Sixt, R. Voituriez, C.-P.J. Heisenberg, Cell 160 (2015) 673–685.","apa":"Ruprecht, V., Wieser, S., Callan Jones, A., Smutny, M., Morita, H., Sako, K., … Heisenberg, C.-P. J. (2015). Cortical contractility triggers a stochastic switch to fast amoeboid cell motility. Cell. Cell Press. https://doi.org/10.1016/j.cell.2015.01.008","ieee":"V. Ruprecht et al., “Cortical contractility triggers a stochastic switch to fast amoeboid cell motility,” Cell, vol. 160, no. 4. Cell Press, pp. 673–685, 2015.","mla":"Ruprecht, Verena, et al. “Cortical Contractility Triggers a Stochastic Switch to Fast Amoeboid Cell Motility.” Cell, vol. 160, no. 4, Cell Press, 2015, pp. 673–85, doi:10.1016/j.cell.2015.01.008."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"issue":"4","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"961"}]},"has_accepted_license":"1","acknowledgement":"We would like to thank R. Hausschild and E. Papusheva for technical assistance and the service facilities at the IST Austria for continuous support. The caRhoA plasmid was a kind gift of T. Kudoh and A. Takesono. We thank M. Piel and E. Paluch for exchanging unpublished data. ","publist_id":"5634","file":[{"relation":"main_file","file_id":"5003","creator":"system","content_type":"application/pdf","file_name":"IST-2016-484-v1+1_1-s2.0-S0092867415000094-main.pdf","checksum":"228d3edf40627d897b3875088a0ac51f","file_size":4362653,"date_created":"2018-12-12T10:13:21Z","date_updated":"2020-07-14T12:45:01Z","access_level":"open_access"}],"status":"public","file_date_updated":"2020-07-14T12:45:01Z","volume":160,"publisher":"Cell Press","article_processing_charge":"No","_id":"1537","author":[{"first_name":"Verena","id":"4D71A03A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4088-8633","full_name":"Ruprecht, Verena","last_name":"Ruprecht"},{"last_name":"Wieser","full_name":"Wieser, Stefan","orcid":"0000-0002-2670-2217","id":"355AA5A0-F248-11E8-B48F-1D18A9856A87","first_name":"Stefan"},{"last_name":"Callan Jones","full_name":"Callan Jones, Andrew","first_name":"Andrew"},{"first_name":"Michael","id":"3FE6E4E8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5920-9090","full_name":"Smutny, Michael","last_name":"Smutny"},{"full_name":"Morita, Hitoshi","last_name":"Morita","first_name":"Hitoshi","id":"4C6E54C6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-6453-8075","first_name":"Keisuke","id":"3BED66BE-F248-11E8-B48F-1D18A9856A87","last_name":"Sako","full_name":"Sako, Keisuke"},{"last_name":"Barone","full_name":"Barone, Vanessa","orcid":"0000-0003-2676-3367","id":"419EECCC-F248-11E8-B48F-1D18A9856A87","first_name":"Vanessa"},{"full_name":"Ritsch Marte, Monika","last_name":"Ritsch Marte","first_name":"Monika"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"},{"first_name":"Raphaël","full_name":"Voituriez, Raphaël","last_name":"Voituriez"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg"}],"department":[{"_id":"CaHe"},{"_id":"MiSi"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","day":"12","year":"2015","date_published":"2015-02-12T00:00:00Z","pubrep_id":"484","oa":1,"intvolume":" 160","isi":1,"ddc":["570"],"month":"02","corr_author":"1","publication":"Cell","page":"673 - 685","date_created":"2018-12-11T11:52:35Z","doi":"10.1016/j.cell.2015.01.008","title":"Cortical contractility triggers a stochastic switch to fast amoeboid cell motility","abstract":[{"lang":"eng","text":"3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype."}],"acknowledged_ssus":[{"_id":"SSU"}],"external_id":{"isi":["000349208800011"]},"scopus_import":"1","publication_status":"published","date_updated":"2026-04-08T14:22:39Z","oa_version":"Published Version","language":[{"iso":"eng"}]}]