[{"status":"public","ddc":["570"],"title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","intvolume":" 57","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10703","oa_version":"Published Version","type":"journal_article","abstract":[{"text":"When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.","lang":"eng"}],"issue":"1","article_type":"original","page":"47-62.e9","publication":"Developmental Cell","citation":{"chicago":"Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024.","short":"F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9.","mla":"Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell, vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024.","apa":"Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. Cell Press ; Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024","ieee":"F. Gaertner et al., “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” Developmental Cell, vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022.","ista":"Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9.","ama":"Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024"},"date_published":"2022-01-10T00:00:00Z","scopus_import":"1","day":"10","article_processing_charge":"No","publication_status":"published","department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}],"publisher":"Cell Press ; Elsevier","year":"2022","acknowledgement":"We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687.","pmid":1,"date_updated":"2024-03-28T23:30:23Z","date_created":"2022-01-30T23:01:33Z","volume":57,"author":[{"first_name":"Florian","last_name":"Gaertner","full_name":"Gaertner, Florian"},{"last_name":"Reis-Rodrigues","first_name":"Patricia","full_name":"Reis-Rodrigues, Patricia"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid"},{"full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","last_name":"Hons","first_name":"Miroslav"},{"first_name":"Juan","last_name":"Aguilera","full_name":"Aguilera, Juan"},{"full_name":"Riedl, Michael","last_name":"Riedl","first_name":"Michael","orcid":"0000-0003-4844-6311","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","first_name":"Alexander F","full_name":"Leithner, Alexander F"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","first_name":"Saren","last_name":"Tasciyan","full_name":"Tasciyan, Saren"},{"full_name":"Kopf, Aglaja","first_name":"Aglaja","last_name":"Kopf","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656"},{"orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","first_name":"Jack","full_name":"Merrin, Jack"},{"full_name":"Zheden, Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9438-4783","first_name":"Vanessa","last_name":"Zheden"},{"full_name":"Kaufmann, Walter","last_name":"Kaufmann","first_name":"Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12726"},{"id":"14530","status":"public","relation":"dissertation_contains"},{"id":"12401","status":"public","relation":"dissertation_contains"}]},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"isi":1,"quality_controlled":"1","project":[{"call_identifier":"H2020","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","grant_number":"747687"},{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"}],"external_id":{"isi":["000768933800005"],"pmid":["34919802"]},"tmp":{"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","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"main_file_link":[{"url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497","open_access":"1"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.devcel.2021.11.024","month":"01","publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]}},{"year":"2020","acknowledgement":"We thank A. Leithner and J. Renkawitz for discussion and critical reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic setups; the Bioimaging Facility of IST Austria for excellent support, as well as the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan, L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme. This work was supported by the European Research Council (ERC StG 281556 and CoG 724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476). F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687.","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"MiSi"}],"author":[{"full_name":"Reversat, Anne","first_name":"Anne","last_name":"Reversat","id":"35B76592-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0666-8928"},{"full_name":"Gärtner, Florian R","last_name":"Gärtner","first_name":"Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","first_name":"Jack","full_name":"Merrin, Jack"},{"full_name":"Stopp, Julian A","last_name":"Stopp","first_name":"Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tasciyan","first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren"},{"first_name":"Juan L","last_name":"Aguilera Servin","id":"2A67C376-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2862-8372","full_name":"Aguilera Servin, Juan L"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"last_name":"Hons","first_name":"Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","full_name":"Hons, Miroslav"},{"full_name":"Piel, Matthieu","first_name":"Matthieu","last_name":"Piel"},{"full_name":"Callan-Jones, Andrew","last_name":"Callan-Jones","first_name":"Andrew"},{"full_name":"Voituriez, Raphael","last_name":"Voituriez","first_name":"Raphael"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"14697"},{"status":"public","relation":"dissertation_contains","id":"12401"}],"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/"}]},"date_created":"2020-05-24T22:01:01Z","date_updated":"2024-03-28T23:30:24Z","volume":582,"ec_funded":1,"external_id":{"isi":["000532688300008"]},"isi":1,"quality_controlled":"1","project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7","grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425"},{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","call_identifier":"H2020","name":"Cellular navigation along spatial gradients"},{"call_identifier":"FWF","name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911","_id":"26018E70-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","grant_number":"747687"}],"doi":"10.1038/s41586-020-2283-z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"language":[{"iso":"eng"}],"month":"06","publication_identifier":{"issn":["00280836"],"eissn":["14764687"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7885","status":"public","title":"Cellular locomotion using environmental topography","intvolume":" 582","oa_version":"None","type":"journal_article","abstract":[{"lang":"eng","text":"Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour."}],"publication":"Nature","citation":{"ama":"Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental topography. Nature. 2020;582:582–585. doi:10.1038/s41586-020-2283-z","apa":"Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography. Nature. Springer Nature. https://doi.org/10.1038/s41586-020-2283-z","ieee":"A. Reversat et al., “Cellular locomotion using environmental topography,” Nature, vol. 582. Springer Nature, pp. 582–585, 2020.","ista":"Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL, de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK. 2020. Cellular locomotion using environmental topography. Nature. 582, 582–585.","short":"A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez, M.K. Sixt, Nature 582 (2020) 582–585.","mla":"Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.” Nature, vol. 582, Springer Nature, 2020, pp. 582–585, doi:10.1038/s41586-020-2283-z.","chicago":"Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan, Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental Topography.” Nature. Springer Nature, 2020. https://doi.org/10.1038/s41586-020-2283-z."},"article_type":"original","page":"582–585","date_published":"2020-06-25T00:00:00Z","scopus_import":"1","day":"25","article_processing_charge":"No"},{"month":"04","doi":"10.1038/s41586-019-1087-5","acknowledged_ssus":[{"_id":"SSU"}],"language":[{"iso":"eng"}],"oa":1,"external_id":{"isi":["000465594200050"],"pmid":["30944468"]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/"}],"isi":1,"quality_controlled":"1","project":[{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"},{"name":"Cellular navigation along spatial gradients","call_identifier":"H2020","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"name":"Nano-Analytics of Cellular Systems","call_identifier":"FWF","_id":"265FAEBA-B435-11E9-9278-68D0E5697425","grant_number":"W01250-B20"},{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"name":"Molecular and system level view of immune cell migration","grant_number":"ALTF 1396-2014","_id":"25A48D24-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"author":[{"full_name":"Renkawitz, Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","first_name":"Jörg"},{"orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","last_name":"Kopf","first_name":"Aglaja","full_name":"Kopf, Aglaja"},{"full_name":"Stopp, Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","last_name":"Stopp","first_name":"Julian A"},{"full_name":"de Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"de Vries"},{"last_name":"Driscoll","first_name":"Meghan K.","full_name":"Driscoll, Meghan K."},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","first_name":"Jack","last_name":"Merrin","full_name":"Merrin, Jack"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Erik S.","last_name":"Welf","full_name":"Welf, Erik S."},{"full_name":"Danuser, Gaudenz","first_name":"Gaudenz","last_name":"Danuser"},{"first_name":"Reto","last_name":"Fiolka","full_name":"Fiolka, Reto"},{"full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/"}],"record":[{"id":"14697","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"6891"}]},"date_created":"2019-04-17T06:52:28Z","date_updated":"2024-03-28T23:30:40Z","volume":568,"year":"2019","pmid":1,"publication_status":"published","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"publisher":"Springer Nature","day":"25","article_processing_charge":"No","scopus_import":"1","date_published":"2019-04-25T00:00:00Z","publication":"Nature","citation":{"ieee":"J. Renkawitz et al., “Nuclear positioning facilitates amoeboid migration along the path of least resistance,” Nature, vol. 568. Springer Nature, pp. 546–550, 2019.","apa":"Renkawitz, J., Kopf, A., Stopp, J. A., de Vries, I., Driscoll, M. K., Merrin, J., … Sixt, M. K. (2019). Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1087-5","ista":"Renkawitz J, Kopf A, Stopp JA, de Vries I, Driscoll MK, Merrin J, Hauschild R, Welf ES, Danuser G, Fiolka R, Sixt MK. 2019. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 568, 546–550.","ama":"Renkawitz J, Kopf A, Stopp JA, et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 2019;568:546-550. doi:10.1038/s41586-019-1087-5","chicago":"Renkawitz, Jörg, Aglaja Kopf, Julian A Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature. Springer Nature, 2019. https://doi.org/10.1038/s41586-019-1087-5.","short":"J. Renkawitz, A. Kopf, J.A. Stopp, I. de Vries, M.K. Driscoll, J. Merrin, R. Hauschild, E.S. Welf, G. Danuser, R. Fiolka, M.K. Sixt, Nature 568 (2019) 546–550.","mla":"Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature, vol. 568, Springer Nature, 2019, pp. 546–50, doi:10.1038/s41586-019-1087-5."},"article_type":"letter_note","page":"546-550","abstract":[{"lang":"eng","text":"During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion."}],"type":"journal_article","oa_version":"Submitted Version","_id":"6328","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","title":"Nuclear positioning facilitates amoeboid migration along the path of least resistance","intvolume":" 568"},{"date_published":"2018-02-13T00:00:00Z","page":"1074 - 1077","publication":"European Journal of Immunology","citation":{"short":"A.F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, M.K. Sixt, European Journal of Immunology 48 (2018) 1074–1077.","mla":"Leithner, Alexander F., et al. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” European Journal of Immunology, vol. 48, no. 6, Wiley-Blackwell, 2018, pp. 1074–77, doi:10.1002/eji.201747358.","chicago":"Leithner, Alexander F, Jörg Renkawitz, Ingrid de Vries, Robert Hauschild, Hans Haecker, and Michael K Sixt. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” European Journal of Immunology. Wiley-Blackwell, 2018. https://doi.org/10.1002/eji.201747358.","ama":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. 2018;48(6):1074-1077. doi:10.1002/eji.201747358","ieee":"A. F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, and M. K. Sixt, “Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration,” European Journal of Immunology, vol. 48, no. 6. Wiley-Blackwell, pp. 1074–1077, 2018.","apa":"Leithner, A. F., Renkawitz, J., de Vries, I., Hauschild, R., Haecker, H., & Sixt, M. K. (2018). Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. Wiley-Blackwell. https://doi.org/10.1002/eji.201747358","ista":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. 2018. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. 48(6), 1074–1077."},"day":"13","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","scopus_import":"1","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"IST-2018-1067-v1+2_Leithner_et_al-2018-European_Journal_of_Immunology.pdf","creator":"system","file_size":590106,"content_type":"application/pdf","file_id":"5044","relation":"main_file","checksum":"9d5b74cd016505aeb9a4c2d33bbedaeb","date_updated":"2020-07-14T12:46:27Z","date_created":"2018-12-12T10:13:56Z"}],"pubrep_id":"1067","title":"Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration","status":"public","ddc":["570"],"intvolume":" 48","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"437","abstract":[{"text":"Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity.","lang":"eng"}],"issue":"6","type":"journal_article","acknowledged_ssus":[{"_id":"SSU"}],"language":[{"iso":"eng"}],"doi":"10.1002/eji.201747358","quality_controlled":"1","isi":1,"project":[{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"external_id":{"isi":["000434963700016"]},"month":"02","date_updated":"2023-09-11T14:01:18Z","date_created":"2018-12-11T11:46:28Z","volume":48,"author":[{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Renkawitz","first_name":"Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","full_name":"Renkawitz, Jörg"},{"last_name":"De Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Hans","last_name":"Haecker","full_name":"Haecker, Hans"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"publication_status":"published","publisher":"Wiley-Blackwell","department":[{"_id":"MiSi"},{"_id":"Bio"}],"year":"2018","acknowledgement":"This work was supported by grants of the European Research Council (ERC CoG 724373) and the Austrian Science Fund (FWF) to M.S. We thank the scientific support units at IST Austria for excellent technical support.\r\nWe thank the scientific support units at IST Austria for excellent technical support. ","license":"https://creativecommons.org/licenses/by-nc/4.0/","file_date_updated":"2020-07-14T12:46:27Z","ec_funded":1,"publist_id":"7386"},{"quality_controlled":"1","isi":1,"oa":1,"tmp":{"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","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"external_id":{"isi":["000440822900011"]},"language":[{"iso":"eng"}],"doi":"10.1084/jem.20170896","month":"06","publication_identifier":{"issn":["0022-1007"],"eissn":["1540-9538"]},"publication_status":"published","publisher":"Rockefeller University Press","department":[{"_id":"MiSi"}],"year":"2018","date_updated":"2023-09-19T14:52:08Z","date_created":"2019-05-28T12:36:47Z","volume":2015,"author":[{"full_name":"Moalli, Federica","first_name":"Federica","last_name":"Moalli"},{"last_name":"Ficht","first_name":"Xenia","full_name":"Ficht, Xenia"},{"last_name":"Germann","first_name":"Philipp","full_name":"Germann, Philipp"},{"first_name":"Mykhailo","last_name":"Vladymyrov","full_name":"Vladymyrov, Mykhailo"},{"first_name":"Bettina","last_name":"Stolp","full_name":"Stolp, Bettina"},{"full_name":"de Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"de Vries","first_name":"Ingrid"},{"last_name":"Lyck","first_name":"Ruth","full_name":"Lyck, Ruth"},{"first_name":"Jasmin","last_name":"Balmer","full_name":"Balmer, Jasmin"},{"last_name":"Fiocchi","first_name":"Amleto","full_name":"Fiocchi, Amleto"},{"first_name":"Mario","last_name":"Kreutzfeldt","full_name":"Kreutzfeldt, Mario"},{"full_name":"Merkler, Doron","first_name":"Doron","last_name":"Merkler"},{"first_name":"Matteo","last_name":"Iannacone","full_name":"Iannacone, Matteo"},{"last_name":"Ariga","first_name":"Akitaka","full_name":"Ariga, Akitaka"},{"full_name":"Stoffel, Michael H.","last_name":"Stoffel","first_name":"Michael H."},{"first_name":"James","last_name":"Sharpe","full_name":"Sharpe, James"},{"first_name":"Martin","last_name":"Bähler","full_name":"Bähler, Martin"},{"last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"},{"full_name":"Diz-Muñoz, Alba","last_name":"Diz-Muñoz","first_name":"Alba"},{"full_name":"Stein, Jens V.","last_name":"Stein","first_name":"Jens V."}],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","file_date_updated":"2020-07-14T12:47:32Z","page":"1869–1890","publication":"The Journal of Experimental Medicine","citation":{"ieee":"F. Moalli et al., “The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells,” The Journal of Experimental Medicine, vol. 2015, no. 7. Rockefeller University Press, pp. 1869–1890, 2018.","apa":"Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., de Vries, I., … Stein, J. V. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. Rockefeller University Press. https://doi.org/10.1084/jem.20170896","ista":"Moalli F, Ficht X, Germann P, Vladymyrov M, Stolp B, de Vries I, Lyck R, Balmer J, Fiocchi A, Kreutzfeldt M, Merkler D, Iannacone M, Ariga A, Stoffel MH, Sharpe J, Bähler M, Sixt MK, Diz-Muñoz A, Stein JV. 2018. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. 2015(7), 1869–1890.","ama":"Moalli F, Ficht X, Germann P, et al. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. 2018;2015(7):1869–1890. doi:10.1084/jem.20170896","chicago":"Moalli, Federica, Xenia Ficht, Philipp Germann, Mykhailo Vladymyrov, Bettina Stolp, Ingrid de Vries, Ruth Lyck, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” The Journal of Experimental Medicine. Rockefeller University Press, 2018. https://doi.org/10.1084/jem.20170896.","short":"F. Moalli, X. Ficht, P. Germann, M. Vladymyrov, B. Stolp, I. de Vries, R. Lyck, J. Balmer, A. Fiocchi, M. Kreutzfeldt, D. Merkler, M. Iannacone, A. Ariga, M.H. Stoffel, J. Sharpe, M. Bähler, M.K. Sixt, A. Diz-Muñoz, J.V. Stein, The Journal of Experimental Medicine 2015 (2018) 1869–1890.","mla":"Moalli, Federica, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” The Journal of Experimental Medicine, vol. 2015, no. 7, Rockefeller University Press, 2018, pp. 1869–1890, doi:10.1084/jem.20170896."},"date_published":"2018-06-06T00:00:00Z","scopus_import":"1","day":"06","article_processing_charge":"No","has_accepted_license":"1","title":"The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells","ddc":["570"],"status":"public","intvolume":" 2015","_id":"6497","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","file":[{"file_name":"2018_rupress_Moalli.pdf","access_level":"open_access","file_size":3841660,"content_type":"application/pdf","creator":"kschuh","relation":"main_file","file_id":"6498","date_created":"2019-05-28T12:40:05Z","date_updated":"2020-07-14T12:47:32Z","checksum":"86ae5331f9bfced9a6358a790a04bef4"}],"type":"journal_article","abstract":[{"text":"T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations.","lang":"eng"}],"issue":"7"},{"publication_identifier":{"issn":["22111247"]},"month":"05","tmp":{"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","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"project":[{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"},{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12"}],"quality_controlled":"1","doi":"10.1016/j.celrep.2017.04.027","language":[{"iso":"eng"}],"ec_funded":1,"publist_id":"7052","file_date_updated":"2020-07-14T12:47:38Z","year":"2017","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"publisher":"Cell Press","publication_status":"published","author":[{"first_name":"Kari","last_name":"Vaahtomeri","id":"368EE576-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7829-3518","full_name":"Vaahtomeri, Kari"},{"id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus"},{"full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries","full_name":"De Vries, Ingrid"},{"last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"orcid":"0000-0001-8599-1226","id":"3C23B994-F248-11E8-B48F-1D18A9856A87","last_name":"Mehling","first_name":"Matthias","full_name":"Mehling, Matthias"},{"first_name":"Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"volume":19,"date_created":"2018-12-11T11:47:50Z","date_updated":"2023-02-23T12:50:09Z","scopus_import":1,"article_processing_charge":"Yes","has_accepted_license":"1","day":"02","citation":{"ama":"Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. 2017;19(5):902-909. doi:10.1016/j.celrep.2017.04.027","apa":"Vaahtomeri, K., Brown, M., Hauschild, R., de Vries, I., Leithner, A. F., Mehling, M., … Sixt, M. K. (2017). Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2017.04.027","ieee":"K. Vaahtomeri et al., “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” Cell Reports, vol. 19, no. 5. Cell Press, pp. 902–909, 2017.","ista":"Vaahtomeri K, Brown M, Hauschild R, de Vries I, Leithner AF, Mehling M, Kaufmann W, Sixt MK. 2017. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. 19(5), 902–909.","short":"K. Vaahtomeri, M. Brown, R. Hauschild, I. de Vries, A.F. Leithner, M. Mehling, W. Kaufmann, M.K. Sixt, Cell Reports 19 (2017) 902–909.","mla":"Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” Cell Reports, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:10.1016/j.celrep.2017.04.027.","chicago":"Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2017.04.027."},"publication":"Cell Reports","page":"902 - 909","date_published":"2017-05-02T00:00:00Z","type":"journal_article","issue":"5","abstract":[{"text":"Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.","lang":"eng"}],"_id":"672","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":" 19","status":"public","ddc":["570"],"title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","pubrep_id":"900","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":2248814,"creator":"system","access_level":"open_access","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf","checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2","date_created":"2018-12-12T10:14:54Z","date_updated":"2020-07-14T12:47:38Z","relation":"main_file","file_id":"5109"}]},{"language":[{"iso":"eng"}],"doi":"10.1016/j.cub.2017.04.004","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","publication_identifier":{"issn":["09609822"]},"month":"05","volume":27,"date_created":"2018-12-11T11:47:51Z","date_updated":"2023-02-23T12:50:44Z","author":[{"full_name":"Schwarz, Jan","first_name":"Jan","last_name":"Schwarz","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bierbaum, Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87","last_name":"Bierbaum","first_name":"Veronika"},{"last_name":"Vaahtomeri","first_name":"Kari","orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari"},{"full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert"},{"first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"},{"last_name":"De Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid"},{"last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"first_name":"Anne","last_name":"Reversat","id":"35B76592-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0666-8928","full_name":"Reversat, Anne"},{"full_name":"Merrin, Jack","last_name":"Merrin","first_name":"Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tarrant, Teresa","last_name":"Tarrant","first_name":"Teresa"},{"last_name":"Bollenbach","first_name":"Tobias","orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias"},{"full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Cell Press","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"publication_status":"published","year":"2017","publist_id":"7050","ec_funded":1,"date_published":"2017-05-09T00:00:00Z","page":"1314 - 1325","citation":{"short":"J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. de Vries, A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, M.T. Bollenbach, M.K. Sixt, Current Biology 27 (2017) 1314–1325.","mla":"Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:10.1016/j.cub.2017.04.004.","chicago":"Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology. Cell Press, 2017. https://doi.org/10.1016/j.cub.2017.04.004.","ama":"Schwarz J, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 2017;27(9):1314-1325. doi:10.1016/j.cub.2017.04.004","ieee":"J. Schwarz et al., “Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6,” Current Biology, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017.","apa":"Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., de Vries, I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2017.04.004","ista":"Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner AF, Reversat A, Merrin J, Tarrant T, Bollenbach MT, Sixt MK. 2017. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325."},"publication":"Current Biology","day":"09","scopus_import":1,"oa_version":"None","intvolume":" 27","title":"Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6","status":"public","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","_id":"674","issue":"9","abstract":[{"text":"Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo.","lang":"eng"}],"type":"journal_article"},{"date_published":"2017-09-21T00:00:00Z","page":"188 - 200","publication":"Cell","citation":{"ama":"Mueller J, Szep G, Nemethova M, et al. Load adaptation of lamellipodial actin networks. Cell. 2017;171(1):188-200. doi:10.1016/j.cell.2017.07.051","apa":"Mueller, J., Szep, G., Nemethova, M., de Vries, I., Lieber, A., Winkler, C., … Sixt, M. K. (2017). Load adaptation of lamellipodial actin networks. Cell. Cell Press. https://doi.org/10.1016/j.cell.2017.07.051","ieee":"J. Mueller et al., “Load adaptation of lamellipodial actin networks,” Cell, vol. 171, no. 1. Cell Press, pp. 188–200, 2017.","ista":"Mueller J, Szep G, Nemethova M, de Vries I, Lieber A, Winkler C, Kruse K, Small J, Schmeiser C, Keren K, Hauschild R, Sixt MK. 2017. Load adaptation of lamellipodial actin networks. Cell. 171(1), 188–200.","short":"J. Mueller, G. Szep, M. Nemethova, I. de Vries, A. Lieber, C. Winkler, K. Kruse, J. Small, C. Schmeiser, K. Keren, R. Hauschild, M.K. Sixt, Cell 171 (2017) 188–200.","mla":"Mueller, Jan, et al. “Load Adaptation of Lamellipodial Actin Networks.” Cell, vol. 171, no. 1, Cell Press, 2017, pp. 188–200, doi:10.1016/j.cell.2017.07.051.","chicago":"Mueller, Jan, Gregory Szep, Maria Nemethova, Ingrid de Vries, Arnon Lieber, Christoph Winkler, Karsten Kruse, et al. “Load Adaptation of Lamellipodial Actin Networks.” Cell. Cell Press, 2017. https://doi.org/10.1016/j.cell.2017.07.051."},"day":"21","article_processing_charge":"No","scopus_import":"1","oa_version":"None","status":"public","title":"Load adaptation of lamellipodial actin networks","intvolume":" 171","_id":"727","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","abstract":[{"text":"Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70° branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.","lang":"eng"}],"issue":"1","type":"journal_article","acknowledged_ssus":[{"_id":"ScienComp"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2017.07.051","quality_controlled":"1","isi":1,"project":[{"name":"Modeling of Polarization and Motility of Leukocytes in Three-Dimensional Environments","_id":"25AD6156-B435-11E9-9278-68D0E5697425","grant_number":"LS13-029"},{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"}],"external_id":{"isi":["000411331800020"]},"month":"09","publication_identifier":{"issn":["00928674"]},"date_updated":"2023-09-28T11:33:49Z","date_created":"2018-12-11T11:48:10Z","volume":171,"author":[{"first_name":"Jan","last_name":"Mueller","full_name":"Mueller, Jan"},{"full_name":"Szep, Gregory","last_name":"Szep","first_name":"Gregory","id":"4BFB7762-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Nemethova, Maria","first_name":"Maria","last_name":"Nemethova","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid"},{"full_name":"Lieber, Arnon","first_name":"Arnon","last_name":"Lieber"},{"first_name":"Christoph","last_name":"Winkler","full_name":"Winkler, Christoph"},{"full_name":"Kruse, Karsten","last_name":"Kruse","first_name":"Karsten"},{"full_name":"Small, John","first_name":"John","last_name":"Small"},{"last_name":"Schmeiser","first_name":"Christian","full_name":"Schmeiser, Christian"},{"full_name":"Keren, Kinneret","last_name":"Keren","first_name":"Kinneret"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"publication_status":"published","publisher":"Cell Press","department":[{"_id":"MiSi"},{"_id":"Bio"}],"year":"2017","ec_funded":1,"publist_id":"6951"},{"ec_funded":1,"publist_id":"5570","year":"2016","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. ","pmid":1,"publication_status":"published","department":[{"_id":"MiSi"}],"publisher":"American Association for the Advancement of Science","author":[{"id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6165-5738","first_name":"Eva","last_name":"Kiermaier","full_name":"Kiermaier, Eva"},{"full_name":"Moussion, Christine","last_name":"Moussion","first_name":"Christine","id":"3356F664-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Veldkamp, Christopher","last_name":"Veldkamp","first_name":"Christopher"},{"full_name":"Gerardy Schahn, Rita","last_name":"Gerardy Schahn","first_name":"Rita"},{"first_name":"Ingrid","last_name":"De Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid"},{"first_name":"Larry","last_name":"Williams","full_name":"Williams, Larry"},{"full_name":"Chaffee, Gary","first_name":"Gary","last_name":"Chaffee"},{"full_name":"Phillips, Andrew","last_name":"Phillips","first_name":"Andrew"},{"full_name":"Freiberger, Friedrich","first_name":"Friedrich","last_name":"Freiberger"},{"full_name":"Imre, Richard","last_name":"Imre","first_name":"Richard"},{"full_name":"Taleski, Deni","first_name":"Deni","last_name":"Taleski"},{"full_name":"Payne, Richard","first_name":"Richard","last_name":"Payne"},{"full_name":"Braun, Asolina","first_name":"Asolina","last_name":"Braun"},{"full_name":"Förster, Reinhold","first_name":"Reinhold","last_name":"Förster"},{"last_name":"Mechtler","first_name":"Karl","full_name":"Mechtler, Karl"},{"full_name":"Mühlenhoff, Martina","first_name":"Martina","last_name":"Mühlenhoff"},{"full_name":"Volkman, Brian","last_name":"Volkman","first_name":"Brian"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"date_updated":"2021-01-12T06:51:52Z","date_created":"2018-12-11T11:52:57Z","volume":351,"month":"01","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/","open_access":"1"}],"oa":1,"external_id":{"pmid":["26657283"]},"quality_controlled":"1","project":[{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425"},{"name":"Stromal Cell-immune Cell Interactions in Health and Disease","call_identifier":"FP7","_id":"25A76F58-B435-11E9-9278-68D0E5697425","grant_number":"289720"},{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12"}],"doi":"10.1126/science.aad0512","acknowledged_ssus":[{"_id":"SSU"}],"language":[{"iso":"eng"}],"type":"journal_article","abstract":[{"lang":"eng","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"}],"issue":"6269","_id":"1599","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","title":"Polysialylation controls dendritic cell trafficking by regulating chemokine recognition","intvolume":" 351","oa_version":"Submitted Version","scopus_import":1,"day":"08","article_processing_charge":"No","publication":"Science","citation":{"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.","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.","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","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.","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.","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"},"article_type":"original","page":"186 - 190","date_published":"2016-01-08T00:00:00Z"},{"project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7"}],"quality_controlled":"1","tmp":{"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","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"oa":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"doi":"10.1038/ncb3426","month":"10","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"publisher":"Nature Publishing Group","publication_status":"published","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.","year":"2016","volume":18,"date_created":"2018-12-11T11:51:21Z","date_updated":"2024-03-28T23:30:16Z","related_material":{"record":[{"id":"323","relation":"dissertation_contains","status":"public"}]},"author":[{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","first_name":"Alexander F","last_name":"Leithner"},{"full_name":"Eichner, Alexander","last_name":"Eichner","first_name":"Alexander","id":"4DFA52AE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Müller, Jan","first_name":"Jan","last_name":"Müller","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D"},{"full_name":"Reversat, Anne","id":"35B76592-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0666-8928","first_name":"Anne","last_name":"Reversat"},{"full_name":"Brown, Markus","last_name":"Brown","first_name":"Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Jan"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","first_name":"Jack","last_name":"Merrin","full_name":"Merrin, Jack"},{"full_name":"De Gorter, David","last_name":"De Gorter","first_name":"David"},{"full_name":"Schur, Florian","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","first_name":"Florian","last_name":"Schur"},{"full_name":"Bayerl, Jonathan","first_name":"Jonathan","last_name":"Bayerl"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries","full_name":"De Vries, Ingrid"},{"full_name":"Wieser, Stefan","orcid":"0000-0002-2670-2217","id":"355AA5A0-F248-11E8-B48F-1D18A9856A87","last_name":"Wieser","first_name":"Stefan"},{"last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"full_name":"Lai, Frank","first_name":"Frank","last_name":"Lai"},{"full_name":"Moser, Markus","last_name":"Moser","first_name":"Markus"},{"full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki","first_name":"Dontscho"},{"last_name":"Rottner","first_name":"Klemens","full_name":"Rottner, Klemens"},{"full_name":"Small, Victor","last_name":"Small","first_name":"Victor"},{"last_name":"Stradal","first_name":"Theresia","full_name":"Stradal, Theresia"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt"}],"publist_id":"5949","ec_funded":1,"file_date_updated":"2020-07-14T12:44:43Z","page":"1253 - 1259","article_type":"original","citation":{"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.","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","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.","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."},"publication":"Nature Cell Biology","date_published":"2016-10-24T00:00:00Z","scopus_import":1,"article_processing_charge":"No","has_accepted_license":"1","day":"24","intvolume":" 18","status":"public","ddc":["570"],"title":"Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes","_id":"1321","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file":[{"file_name":"2018_NatureCell_Leithner.pdf","access_level":"open_access","file_size":4433280,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"7844","date_updated":"2020-07-14T12:44:43Z","date_created":"2020-05-14T16:33:46Z","checksum":"e1411cb7c99a2d9089c178a6abef25e7"}],"oa_version":"Submitted Version","type":"journal_article","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."}]},{"day":"01","month":"06","scopus_import":1,"language":[{"iso":"eng"}],"doi":"10.1002/eji.201545457","date_published":"2015-06-01T00:00:00Z","page":"1614 - 1620","quality_controlled":"1","citation":{"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.","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.","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.","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.","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"},"publication":"European Journal of Immunology","publist_id":"5610","issue":"6","abstract":[{"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.","lang":"eng"}],"type":"journal_article","volume":45,"oa_version":"None","date_created":"2018-12-11T11:52:44Z","date_updated":"2021-01-12T06:51:36Z","author":[{"full_name":"Heger, Klaus","first_name":"Klaus","last_name":"Heger"},{"full_name":"Kober, Maike","first_name":"Maike","last_name":"Kober"},{"full_name":"Rieß, David","first_name":"David","last_name":"Rieß"},{"full_name":"Drees, Christoph","last_name":"Drees","first_name":"Christoph"},{"full_name":"De Vries, Ingrid","first_name":"Ingrid","last_name":"De Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bertossi, Arianna","first_name":"Arianna","last_name":"Bertossi"},{"first_name":"Axel","last_name":"Roers","full_name":"Roers, Axel"},{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"},{"first_name":"Marc","last_name":"Schmidt Supprian","full_name":"Schmidt Supprian, Marc"}],"publisher":"Wiley","intvolume":" 45","department":[{"_id":"MiSi"}],"title":"A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors","publication_status":"published","status":"public","year":"2015","_id":"1561","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"abstract":[{"lang":"eng","text":"Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues."}],"issue":"6117","type":"journal_article","oa_version":"Published Version","_id":"2839","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","title":"Interstitial dendritic cell guidance by haptotactic chemokine gradients","intvolume":" 339","day":"18","article_processing_charge":"No","scopus_import":"1","date_published":"2013-01-18T00:00:00Z","publication":"Science","citation":{"ama":"Weber M, Hauschild R, Schwarz J, et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. 2013;339(6117):328-332. doi:10.1126/science.1228456","ista":"Weber M, Hauschild R, Schwarz J, Moussion C, de Vries I, Legler D, Luther S, Bollenbach MT, Sixt MK. 2013. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. 339(6117), 328–332.","ieee":"M. Weber et al., “Interstitial dendritic cell guidance by haptotactic chemokine gradients,” Science, vol. 339, no. 6117. American Association for the Advancement of Science, pp. 328–332, 2013.","apa":"Weber, M., Hauschild, R., Schwarz, J., Moussion, C., de Vries, I., Legler, D., … Sixt, M. K. (2013). Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1228456","mla":"Weber, Michele, et al. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” Science, vol. 339, no. 6117, American Association for the Advancement of Science, 2013, pp. 328–32, doi:10.1126/science.1228456.","short":"M. Weber, R. Hauschild, J. Schwarz, C. Moussion, I. de Vries, D. Legler, S. Luther, M.T. Bollenbach, M.K. Sixt, Science 339 (2013) 328–332.","chicago":"Weber, Michele, Robert Hauschild, Jan Schwarz, Christine Moussion, Ingrid de Vries, Daniel Legler, Sanjiv Luther, Mark Tobias Bollenbach, and Michael K Sixt. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” Science. American Association for the Advancement of Science, 2013. https://doi.org/10.1126/science.1228456."},"article_type":"original","page":"328 - 332","publist_id":"3959","ec_funded":1,"author":[{"full_name":"Weber, Michele","first_name":"Michele","last_name":"Weber","id":"3A3FC708-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Jan","full_name":"Schwarz, Jan"},{"last_name":"Moussion","first_name":"Christine","id":"3356F664-F248-11E8-B48F-1D18A9856A87","full_name":"Moussion, Christine"},{"last_name":"De Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid"},{"last_name":"Legler","first_name":"Daniel","full_name":"Legler, Daniel"},{"last_name":"Luther","first_name":"Sanjiv","full_name":"Luther, Sanjiv"},{"full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","first_name":"Mark Tobias","orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt"}],"date_updated":"2022-06-10T10:21:40Z","date_created":"2018-12-11T11:59:52Z","volume":339,"year":"2013","acknowledgement":"We thank M. Frank for technical assistance and S. Cremer, P. Schmalhorst, and E. Kiermaier for critical reading of the manuscript. This work was supported by a Humboldt Foundation postdoctoral fellowship (to M.W.), the German Research Foundation (Si1323 1,2 to M.S.), the Human Frontier Science Program (HFSP RGP0058/2011 to M.S.), the European Research Council (ERC StG 281556 to M.S.), and the Swiss National Science Foundation (31003A 127474 to D.F.L., 130488 to S.A.L.).","publication_status":"published","department":[{"_id":"MiSi"},{"_id":"Bio"}],"publisher":"American Association for the Advancement of Science","month":"01","doi":"10.1126/science.1228456","language":[{"iso":"eng"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://kops.uni-konstanz.de/bitstream/123456789/26341/2/Weber_263418.pdf"}],"quality_controlled":"1","project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7","grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425"},{"_id":"25ABD200-B435-11E9-9278-68D0E5697425","grant_number":"RGP0058/2011","name":"Cell migration in complex environments: from in vivo experiments to theoretical models"}]}]