[{"external_id":{"isi":["000627134400001"],"pmid":["33717158"]},"_id":"9259","abstract":[{"lang":"eng","text":"Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient."}],"language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","day":"25","citation":{"apa":"Vaahtomeri, K., Moussion, C., Hauschild, R., &#38; Sixt, M. K. (2021). Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. <i>Frontiers in Immunology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fimmu.2021.630002\">https://doi.org/10.3389/fimmu.2021.630002</a>","mla":"Vaahtomeri, Kari, et al. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” <i>Frontiers in Immunology</i>, vol. 12, 630002, Frontiers, 2021, doi:<a href=\"https://doi.org/10.3389/fimmu.2021.630002\">10.3389/fimmu.2021.630002</a>.","ieee":"K. Vaahtomeri, C. Moussion, R. Hauschild, and M. K. Sixt, “Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium,” <i>Frontiers in Immunology</i>, vol. 12. Frontiers, 2021.","short":"K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology 12 (2021).","chicago":"Vaahtomeri, Kari, Christine Moussion, Robert Hauschild, and Michael K Sixt. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” <i>Frontiers in Immunology</i>. Frontiers, 2021. <a href=\"https://doi.org/10.3389/fimmu.2021.630002\">https://doi.org/10.3389/fimmu.2021.630002</a>.","ama":"Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. <i>Frontiers in Immunology</i>. 2021;12. doi:<a href=\"https://doi.org/10.3389/fimmu.2021.630002\">10.3389/fimmu.2021.630002</a>","ista":"Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. 12, 630002."},"has_accepted_license":"1","article_number":"630002","intvolume":"        12","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"year":"2021","date_published":"2021-02-25T00:00:00Z","file_date_updated":"2021-03-22T12:08:26Z","date_updated":"2025-04-14T07:42:07Z","publication":"Frontiers in Immunology","isi":1,"status":"public","license":"https://creativecommons.org/licenses/by/4.0/","ec_funded":1,"scopus_import":"1","publication_status":"published","file":[{"relation":"main_file","creator":"dernst","file_id":"9277","date_updated":"2021-03-22T12:08:26Z","file_name":"2021_FrontiersImmumo_Vaahtomeri.pdf","checksum":"663f5a48375e42afa4bfef58d42ec186","date_created":"2021-03-22T12:08:26Z","file_size":3740146,"success":1,"content_type":"application/pdf","access_level":"open_access"}],"publication_identifier":{"eissn":["1664-3224"]},"title":"Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium","date_created":"2021-03-21T23:01:20Z","oa_version":"Published Version","oa":1,"doi":"10.3389/fimmu.2021.630002","acknowledgement":"This work was supported by Sigrid Juselius fellowship (KV), University of Helsinki 3-year research grant (KV), Academy of Finland Research fellow funding (315710, to KV), the European Research Council (ERC CoG 724373 to MS), and by the Austrian Science foundation (FWF) (Y564-B12 START award to MS).\r\nTaija Mäkinen is acknowledged for providing Prox1CreERT2 transgenic mice and Yu Yamaguchi for providing the conditional Ext1 mouse strain.","author":[{"orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87","first_name":"Kari","last_name":"Vaahtomeri","full_name":"Vaahtomeri, Kari"},{"id":"3356F664-F248-11E8-B48F-1D18A9856A87","first_name":"Christine","last_name":"Moussion","full_name":"Moussion, Christine"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","orcid":"0000-0001-9843-3522"},{"full_name":"Sixt, Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"volume":12,"department":[{"_id":"MiSi"},{"_id":"Bio"}],"month":"02","article_type":"original","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"article_processing_charge":"No","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"Frontiers","pmid":1},{"oa":1,"doi":"10.1083/jcb.201612051","acknowledgement":"M. Brown was supported by the Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund and Medizinische Universität Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung and Advanced European Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland postdoctoral research grant (287853). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668036 (RELENT).","volume":217,"author":[{"last_name":"Brown","full_name":"Brown, Markus","first_name":"Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Louise","full_name":"Johnson, Louise","last_name":"Johnson"},{"first_name":"Dario","full_name":"Leone, Dario","last_name":"Leone"},{"last_name":"Májek","full_name":"Májek, Peter","first_name":"Peter"},{"full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri","orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87","first_name":"Kari"},{"first_name":"Daniel","full_name":"Senfter, Daniel","last_name":"Senfter"},{"last_name":"Bukosza","full_name":"Bukosza, Nora","first_name":"Nora"},{"first_name":"Helga","last_name":"Schachner","full_name":"Schachner, Helga"},{"last_name":"Asfour","full_name":"Asfour, Gabriele","first_name":"Gabriele"},{"first_name":"Brigitte","last_name":"Langer","full_name":"Langer, Brigitte"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","full_name":"Hauschild, Robert","last_name":"Hauschild"},{"first_name":"Katja","last_name":"Parapatics","full_name":"Parapatics, Katja"},{"full_name":"Hong, Young","last_name":"Hong","first_name":"Young"},{"first_name":"Keiryn","last_name":"Bennett","full_name":"Bennett, Keiryn"},{"first_name":"Renate","last_name":"Kain","full_name":"Kain, Renate"},{"last_name":"Detmar","full_name":"Detmar, Michael","first_name":"Michael"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"},{"first_name":"David","full_name":"Jackson, David","last_name":"Jackson"},{"last_name":"Kerjaschki","full_name":"Kerjaschki, Dontscho","first_name":"Dontscho"}],"month":"04","department":[{"_id":"MiSi"},{"_id":"Bio"}],"project":[{"call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","publisher":"Rockefeller University Press","pmid":1,"publication_status":"published","publist_id":"7627","file":[{"content_type":"application/pdf","file_size":2252043,"date_created":"2018-12-17T12:50:07Z","access_level":"open_access","relation":"main_file","file_id":"5704","creator":"dernst","date_updated":"2020-07-14T12:45:45Z","checksum":"9c7eba51a35c62da8c13f98120b64df4","file_name":"2018_JournalCellBiology_Brown.pdf"}],"title":"Lymphatic exosomes promote dendritic cell migration along guidance cues","date_created":"2018-12-11T11:45:33Z","oa_version":"Published Version","file_date_updated":"2020-07-14T12:45:45Z","publication":"Journal of Cell Biology","date_updated":"2025-04-14T13:10:20Z","isi":1,"page":"2205 - 2221","status":"public","issue":"6","ec_funded":1,"scopus_import":"1","external_id":{"isi":["000438077800026"],"pmid":["29650776"]},"_id":"275","abstract":[{"text":"Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified &gt; 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.","lang":"eng"}],"language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","day":"12","citation":{"apa":"Brown, M., Johnson, L., Leone, D., Májek, P., Vaahtomeri, K., Senfter, D., … Kerjaschki, D. (2018). Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>","ieee":"M. Brown <i>et al.</i>, “Lymphatic exosomes promote dendritic cell migration along guidance cues,” <i>Journal of Cell Biology</i>, vol. 217, no. 6. Rockefeller University Press, pp. 2205–2221, 2018.","short":"M. Brown, L. Johnson, D. Leone, P. Májek, K. Vaahtomeri, D. Senfter, N. Bukosza, H. Schachner, G. Asfour, B. Langer, R. Hauschild, K. Parapatics, Y. Hong, K. Bennett, R. Kain, M. Detmar, M.K. Sixt, D. Jackson, D. Kerjaschki, Journal of Cell Biology 217 (2018) 2205–2221.","mla":"Brown, Markus, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>, vol. 217, no. 6, Rockefeller University Press, 2018, pp. 2205–21, doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>.","chicago":"Brown, Markus, Louise Johnson, Dario Leone, Peter Májek, Kari Vaahtomeri, Daniel Senfter, Nora Bukosza, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>.","ista":"Brown M, Johnson L, Leone D, Májek P, Vaahtomeri K, Senfter D, Bukosza N, Schachner H, Asfour G, Langer B, Hauschild R, Parapatics K, Hong Y, Bennett K, Kain R, Detmar M, Sixt MK, Jackson D, Kerjaschki D. 2018. Lymphatic exosomes promote dendritic cell migration along guidance cues. Journal of Cell Biology. 217(6), 2205–2221.","ama":"Brown M, Johnson L, Leone D, et al. Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. 2018;217(6):2205-2221. doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>"},"has_accepted_license":"1","intvolume":"       217","ddc":["570"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2018","date_published":"2018-04-12T00:00:00Z"},{"date_updated":"2026-04-27T22:30:47Z","publication":"Science","isi":1,"acknowledged_ssus":[{"_id":"Bio"}],"status":"public","page":"1408 - 1411","issue":"6382","ec_funded":1,"scopus_import":"1","external_id":{"isi":["000428043600047"],"pmid":["29567714"]},"_id":"402","language":[{"iso":"eng"}],"abstract":[{"text":"During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.","lang":"eng"}],"quality_controlled":"1","type":"journal_article","day":"23","citation":{"ieee":"M. Brown <i>et al.</i>, “Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice,” <i>Science</i>, vol. 359, no. 6382. American Association for the Advancement of Science, pp. 1408–1411, 2018.","short":"M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z. Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018) 1408–1411.","mla":"Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>, vol. 359, no. 6382, American Association for the Advancement of Science, 2018, pp. 1408–11, doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>.","apa":"Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G., … Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>","ista":"Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382), 1408–1411.","ama":"Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. 2018;359(6382):1408-1411. doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>","chicago":"Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner, Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>. American Association for the Advancement of Science, 2018. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>."},"intvolume":"       359","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2018","date_published":"2018-03-23T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1126/science.aal3662"}],"oa":1,"doi":"10.1126/science.aal3662","acknowledgement":"M.B. was supported by the Cell Communication in Health and Disease graduate study program of the Austrian Science Fund (FWF) and the Medical University of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556) and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging, the Sixt lab for intellectual input, M. Schunn for help with the design of the in vivo experiments, F. Langer for technical assistance with the in vivo experiments, the bioimaging facility of IST Austria for support, and R. Efferl for providing the CT26 cell line.","volume":359,"author":[{"full_name":"Brown, Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus"},{"orcid":"0000-0003-3470-6119","first_name":"Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","last_name":"Assen","full_name":"Assen, Frank P"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jun","full_name":"Abe, Jun","last_name":"Abe"},{"last_name":"Schachner","full_name":"Schachner, Helga","first_name":"Helga"},{"first_name":"Gabriele","last_name":"Asfour","full_name":"Asfour, Gabriele"},{"first_name":"Zsuzsanna","last_name":"Bagó Horváth","full_name":"Bagó Horváth, Zsuzsanna"},{"first_name":"Jens","last_name":"Stein","full_name":"Stein, Jens"},{"full_name":"Uhrin, Pavel","last_name":"Uhrin","first_name":"Pavel"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","full_name":"Sixt, Michael K","last_name":"Sixt"},{"full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki","first_name":"Dontscho"}],"department":[{"_id":"MiSi"}],"month":"03","article_type":"original","project":[{"grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"},{"grant_number":"281556","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"}],"article_processing_charge":"No","corr_author":"1","publisher":"American Association for the Advancement of Science","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6947"}]},"pmid":1,"publication_status":"published","publist_id":"7428","title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","date_created":"2018-12-11T11:46:16Z","oa_version":"Published Version"},{"publisher":"Cell Press","corr_author":"1","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","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"},"article_processing_charge":"Yes","project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"month":"05","author":[{"orcid":"0000-0001-7829-3518","first_name":"Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri"},{"first_name":"Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus","last_name":"Brown"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","last_name":"Hauschild"},{"first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","full_name":"De Vries, Ingrid"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F"},{"first_name":"Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8599-1226","full_name":"Mehling, Matthias","last_name":"Mehling"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"volume":19,"pubrep_id":"900","oa":1,"doi":"10.1016/j.celrep.2017.04.027","oa_version":"Published Version","title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","date_created":"2018-12-11T11:47:50Z","publication_identifier":{"issn":["2211-1247"]},"file":[{"file_size":2248814,"date_created":"2018-12-12T10:14:54Z","content_type":"application/pdf","access_level":"open_access","creator":"system","file_id":"5109","relation":"main_file","date_updated":"2020-07-14T12:47:38Z","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf","checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2"}],"publist_id":"7052","publication_status":"published","scopus_import":"1","issue":"5","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","page":"902 - 909","status":"public","isi":1,"date_updated":"2025-09-10T14:27:34Z","publication":"Cell Reports","file_date_updated":"2020-07-14T12:47:38Z","date_published":"2017-05-02T00:00:00Z","year":"2017","ddc":["570"],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","intvolume":"        19","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. <i>Cell Reports</i>. 2017;19(5):902-909. doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>","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.","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.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>.","mla":"Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>.","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.","ieee":"K. Vaahtomeri <i>et al.</i>, “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” <i>Cell Reports</i>, vol. 19, no. 5. Cell Press, pp. 902–909, 2017.","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. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>"},"type":"journal_article","quality_controlled":"1","_id":"672","language":[{"iso":"eng"}],"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"}],"external_id":{"isi":["000402124100002"]}},{"abstract":[{"lang":"eng","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."}],"_id":"674","language":[{"iso":"eng"}],"external_id":{"isi":["000400741700021"]},"type":"journal_article","quality_controlled":"1","citation":{"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. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">https://doi.org/10.1016/j.cub.2017.04.004</a>","ieee":"J. Schwarz <i>et al.</i>, “Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6,” <i>Current Biology</i>, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017.","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.” <i>Current Biology</i>, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:<a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">10.1016/j.cub.2017.04.004</a>.","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.” <i>Current Biology</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">https://doi.org/10.1016/j.cub.2017.04.004</a>.","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.","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. <i>Current Biology</i>. 2017;27(9):1314-1325. doi:<a href=\"https://doi.org/10.1016/j.cub.2017.04.004\">10.1016/j.cub.2017.04.004</a>"},"day":"09","intvolume":"        27","year":"2017","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2017-05-09T00:00:00Z","date_updated":"2025-09-10T14:26:47Z","publication":"Current Biology","isi":1,"page":"1314 - 1325","status":"public","issue":"9","ec_funded":1,"scopus_import":"1","publist_id":"7050","publication_status":"published","publication_identifier":{"issn":["09609822"]},"title":"Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6","date_created":"2018-12-11T11:47:51Z","oa_version":"None","doi":"10.1016/j.cub.2017.04.004","volume":27,"author":[{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan","last_name":"Schwarz","full_name":"Schwarz, Jan"},{"first_name":"Veronika","id":"3FD04378-F248-11E8-B48F-1D18A9856A87","full_name":"Bierbaum, Veronika","last_name":"Bierbaum"},{"full_name":"Vaahtomeri, Kari","last_name":"Vaahtomeri","id":"368EE576-F248-11E8-B48F-1D18A9856A87","first_name":"Kari","orcid":"0000-0001-7829-3518"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","orcid":"0000-0001-9843-3522"},{"full_name":"Brown, Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","full_name":"De Vries, Ingrid","last_name":"De Vries"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X"},{"last_name":"Reversat","full_name":"Reversat, Anne","orcid":"0000-0003-0666-8928","first_name":"Anne","id":"35B76592-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Merrin, Jack","last_name":"Merrin","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"first_name":"Teresa","full_name":"Tarrant, Teresa","last_name":"Tarrant"},{"last_name":"Bollenbach","full_name":"Bollenbach, Tobias","orcid":"0000-0003-4398-476X","first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K"}],"project":[{"name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734"},{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"Y 564-B12","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"month":"05","corr_author":"1","article_processing_charge":"No","publisher":"Cell Press"},{"pubrep_id":"744","doi":"10.1038/srep36440","oa":1,"acknowledgement":"This work was supported by the Swiss National Science Foundation (Ambizione fellowship; PZ00P3-154733 to M.M.), the Swiss Multiple Sclerosis Society (research support to M.M.), a fellowship from the Boehringer Ingelheim Fonds (BIF) to J.S., the European Research Council (grant ERC GA 281556) and a START award from the Austrian Science Foundation (FWF) to M.S. #BioimagingFacility","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"ToBo"}],"month":"11","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"},{"grant_number":"Y 564-B12","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"}],"author":[{"full_name":"Schwarz, Jan","last_name":"Schwarz","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan"},{"full_name":"Bierbaum, Veronika","last_name":"Bierbaum","id":"3FD04378-F248-11E8-B48F-1D18A9856A87","first_name":"Veronika"},{"last_name":"Merrin","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Frank, Tino","last_name":"Frank","first_name":"Tino"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","orcid":"0000-0001-9843-3522"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach","full_name":"Bollenbach, Mark Tobias"},{"full_name":"Tay, Savaş","last_name":"Tay","first_name":"Savaş"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"},{"full_name":"Mehling, Matthias","last_name":"Mehling","orcid":"0000-0001-8599-1226","id":"3C23B994-F248-11E8-B48F-1D18A9856A87","first_name":"Matthias"}],"volume":6,"publisher":"Nature Publishing Group","article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publication_status":"published","publist_id":"6204","file":[{"access_level":"open_access","content_type":"application/pdf","date_created":"2018-12-12T10:09:32Z","file_size":2353456,"file_name":"IST-2017-744-v1+1_srep36440.pdf","relation":"main_file","date_updated":"2018-12-12T10:09:32Z","file_id":"4756","creator":"system"}],"oa_version":"Published Version","title":"A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients","date_created":"2018-12-11T11:50:27Z","file_date_updated":"2018-12-12T10:09:32Z","isi":1,"publication":"Scientific Reports","date_updated":"2025-09-22T09:56:13Z","status":"public","scopus_import":"1","ec_funded":1,"quality_controlled":"1","type":"journal_article","external_id":{"isi":["000387118300001"]},"_id":"1154","abstract":[{"text":"Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines. The majority of data on chemokine gradient sensing is based on in vitro studies employing soluble gradients. Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. We tracked migration of dendritic cells towards immobilized gradients of the chemokine CCL21 and varying superimposed soluble gradients of CCL19. Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. Beyond chemokines our approach is broadly applicable to alternative systems of chemo- and haptotaxis such as cells migrating along gradients of adhesion receptor ligands vs. any soluble cue. \r\n","lang":"eng"}],"language":[{"iso":"eng"}],"citation":{"apa":"Schwarz, J., Bierbaum, V., Merrin, J., Frank, T., Hauschild, R., Bollenbach, M. T., … Mehling, M. (2016). A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/srep36440\">https://doi.org/10.1038/srep36440</a>","short":"J. Schwarz, V. Bierbaum, J. Merrin, T. Frank, R. Hauschild, M.T. Bollenbach, S. Tay, M.K. Sixt, M. Mehling, Scientific Reports 6 (2016).","ieee":"J. Schwarz <i>et al.</i>, “A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients,” <i>Scientific Reports</i>, vol. 6. Nature Publishing Group, 2016.","mla":"Schwarz, Jan, et al. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>, vol. 6, 36440, Nature Publishing Group, 2016, doi:<a href=\"https://doi.org/10.1038/srep36440\">10.1038/srep36440</a>.","chicago":"Schwarz, Jan, Veronika Bierbaum, Jack Merrin, Tino Frank, Robert Hauschild, Mark Tobias Bollenbach, Savaş Tay, Michael K Sixt, and Matthias Mehling. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/srep36440\">https://doi.org/10.1038/srep36440</a>.","ista":"Schwarz J, Bierbaum V, Merrin J, Frank T, Hauschild R, Bollenbach MT, Tay S, Sixt MK, Mehling M. 2016. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. Scientific Reports. 6, 36440.","ama":"Schwarz J, Bierbaum V, Merrin J, et al. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>. 2016;6. doi:<a href=\"https://doi.org/10.1038/srep36440\">10.1038/srep36440</a>"},"day":"07","has_accepted_license":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","ddc":["579"],"year":"2016","article_number":"36440","intvolume":"         6","date_published":"2016-11-07T00:00:00Z"},{"publication_status":"published","publist_id":"6031","oa_version":"None","title":"Focal adhesion-independent cell migration","date_created":"2018-12-11T11:51:08Z","department":[{"_id":"MiSi"}],"month":"10","project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"281556"},{"call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"}],"volume":32,"author":[{"first_name":"Ewa","last_name":"Paluch","full_name":"Paluch, Ewa"},{"full_name":"Aspalter, Irene","last_name":"Aspalter","first_name":"Irene"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K"}],"doi":"10.1146/annurev-cellbio-111315-125341","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.).","publisher":"Annual Reviews","article_processing_charge":"No","citation":{"chicago":"Paluch, Ewa, Irene Aspalter, and Michael K Sixt. “Focal Adhesion-Independent Cell Migration.” <i>Annual Review of Cell and Developmental Biology</i>. Annual Reviews, 2016. <a href=\"https://doi.org/10.1146/annurev-cellbio-111315-125341\">https://doi.org/10.1146/annurev-cellbio-111315-125341</a>.","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. <i>Annual Review of Cell and Developmental Biology</i>. 2016;32:469-490. doi:<a href=\"https://doi.org/10.1146/annurev-cellbio-111315-125341\">10.1146/annurev-cellbio-111315-125341</a>","apa":"Paluch, E., Aspalter, I., &#38; Sixt, M. K. (2016). Focal adhesion-independent cell migration. <i>Annual Review of Cell and Developmental Biology</i>. Annual Reviews. <a href=\"https://doi.org/10.1146/annurev-cellbio-111315-125341\">https://doi.org/10.1146/annurev-cellbio-111315-125341</a>","short":"E. Paluch, I. Aspalter, M.K. Sixt, Annual Review of Cell and Developmental Biology 32 (2016) 469–490.","ieee":"E. Paluch, I. Aspalter, and M. K. Sixt, “Focal adhesion-independent cell migration,” <i>Annual Review of Cell and Developmental Biology</i>, vol. 32. Annual Reviews, pp. 469–490, 2016.","mla":"Paluch, Ewa, et al. “Focal Adhesion-Independent Cell Migration.” <i>Annual Review of Cell and Developmental Biology</i>, vol. 32, Annual Reviews, 2016, pp. 469–90, doi:<a href=\"https://doi.org/10.1146/annurev-cellbio-111315-125341\">10.1146/annurev-cellbio-111315-125341</a>."},"day":"06","quality_controlled":"1","type":"journal_article","external_id":{"isi":["000389576900019"]},"abstract":[{"lang":"eng","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."}],"_id":"1285","language":[{"iso":"eng"}],"date_published":"2016-10-06T00:00:00Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","year":"2016","intvolume":"        32","isi":1,"publication":"Annual Review of Cell and Developmental Biology","date_updated":"2025-09-22T08:33:40Z","scopus_import":"1","ec_funded":1,"status":"public","page":"469 - 490"},{"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","year":"2016","intvolume":"       570","date_published":"2016-01-01T00:00:00Z","quality_controlled":"1","type":"journal_article","external_id":{"pmid":["26921962"],"isi":["000375648700025"]},"_id":"1597","language":[{"iso":"eng"}],"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"}],"day":"01","citation":{"chicago":"Schwarz, Jan, and Michael K Sixt. “Quantitative Analysis of Dendritic Cell Haptotaxis.” <i>Methods in Enzymology</i>. Elsevier, 2016. <a href=\"https://doi.org/10.1016/bs.mie.2015.11.004\">https://doi.org/10.1016/bs.mie.2015.11.004</a>.","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. <i>Methods in Enzymology</i>. 2016;570:567-581. doi:<a href=\"https://doi.org/10.1016/bs.mie.2015.11.004\">10.1016/bs.mie.2015.11.004</a>","apa":"Schwarz, J., &#38; Sixt, M. K. (2016). Quantitative analysis of dendritic cell haptotaxis. <i>Methods in Enzymology</i>. Elsevier. <a href=\"https://doi.org/10.1016/bs.mie.2015.11.004\">https://doi.org/10.1016/bs.mie.2015.11.004</a>","ieee":"J. Schwarz and M. K. Sixt, “Quantitative analysis of dendritic cell haptotaxis,” <i>Methods in Enzymology</i>, vol. 570. Elsevier, pp. 567–581, 2016.","short":"J. Schwarz, M.K. Sixt, Methods in Enzymology 570 (2016) 567–581.","mla":"Schwarz, Jan, and Michael K. Sixt. “Quantitative Analysis of Dendritic Cell Haptotaxis.” <i>Methods in Enzymology</i>, vol. 570, Elsevier, 2016, pp. 567–81, doi:<a href=\"https://doi.org/10.1016/bs.mie.2015.11.004\">10.1016/bs.mie.2015.11.004</a>."},"status":"public","page":"567 - 581","scopus_import":"1","ec_funded":1,"isi":1,"acknowledged_ssus":[{"_id":"Bio"}],"date_updated":"2025-09-18T11:02:13Z","publication":"Methods in Enzymology","oa_version":"None","date_created":"2018-12-11T11:52:56Z","title":"Quantitative analysis of dendritic cell haptotaxis","publication_status":"published","publist_id":"5573","publisher":"Elsevier","article_processing_charge":"No","corr_author":"1","pmid":1,"doi":"10.1016/bs.mie.2015.11.004","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.","department":[{"_id":"MiSi"}],"month":"01","article_type":"original","project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"}],"volume":570,"author":[{"last_name":"Schwarz","full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"}]},{"ec_funded":1,"issue":"6269","scopus_import":"1","status":"public","page":"186 - 190","date_updated":"2025-09-18T11:01:30Z","publication":"Science","isi":1,"acknowledged_ssus":[{"_id":"SSU"}],"date_published":"2016-01-08T00:00:00Z","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/","open_access":"1"}],"intvolume":"       351","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","year":"2016","citation":{"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. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.aad0512\">https://doi.org/10.1126/science.aad0512</a>","mla":"Kiermaier, Eva, et al. “Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” <i>Science</i>, vol. 351, no. 6269, American Association for the Advancement of Science, 2016, pp. 186–90, doi:<a href=\"https://doi.org/10.1126/science.aad0512\">10.1126/science.aad0512</a>.","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.","ieee":"E. Kiermaier <i>et al.</i>, “Polysialylation controls dendritic cell trafficking by regulating chemokine recognition,” <i>Science</i>, vol. 351, no. 6269. American Association for the Advancement of Science, pp. 186–190, 2016.","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.” <i>Science</i>. American Association for the Advancement of Science, 2016. <a href=\"https://doi.org/10.1126/science.aad0512\">https://doi.org/10.1126/science.aad0512</a>.","ama":"Kiermaier E, Moussion C, Veldkamp C, et al. Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. <i>Science</i>. 2016;351(6269):186-190. doi:<a href=\"https://doi.org/10.1126/science.aad0512\">10.1126/science.aad0512</a>","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."},"day":"08","external_id":{"pmid":["26657283"],"isi":["000367806500045"]},"_id":"1599","language":[{"iso":"eng"}],"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"}],"quality_controlled":"1","type":"journal_article","pmid":1,"article_processing_charge":"No","corr_author":"1","publisher":"American Association for the Advancement of Science","author":[{"last_name":"Kiermaier","full_name":"Kiermaier, Eva","orcid":"0000-0001-6165-5738","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","first_name":"Eva"},{"last_name":"Moussion","full_name":"Moussion, Christine","first_name":"Christine","id":"3356F664-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Veldkamp, Christopher","last_name":"Veldkamp","first_name":"Christopher"},{"last_name":"Gerardy  Schahn","full_name":"Gerardy  Schahn, Rita","first_name":"Rita"},{"full_name":"De Vries, Ingrid","last_name":"De Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Williams, Larry","last_name":"Williams","first_name":"Larry"},{"last_name":"Chaffee","full_name":"Chaffee, Gary","first_name":"Gary"},{"first_name":"Andrew","full_name":"Phillips, Andrew","last_name":"Phillips"},{"full_name":"Freiberger, Friedrich","last_name":"Freiberger","first_name":"Friedrich"},{"full_name":"Imre, Richard","last_name":"Imre","first_name":"Richard"},{"first_name":"Deni","last_name":"Taleski","full_name":"Taleski, Deni"},{"first_name":"Richard","full_name":"Payne, Richard","last_name":"Payne"},{"first_name":"Asolina","full_name":"Braun, Asolina","last_name":"Braun"},{"last_name":"Förster","full_name":"Förster, Reinhold","first_name":"Reinhold"},{"last_name":"Mechtler","full_name":"Mechtler, Karl","first_name":"Karl"},{"first_name":"Martina","full_name":"Mühlenhoff, Martina","last_name":"Mühlenhoff"},{"first_name":"Brian","full_name":"Volkman, Brian","last_name":"Volkman"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"volume":351,"department":[{"_id":"MiSi"}],"month":"01","article_type":"original","project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"},{"name":"Stromal Cell-immune Cell Interactions in Health and Disease","call_identifier":"FP7","_id":"25A76F58-B435-11E9-9278-68D0E5697425","grant_number":"289720"},{"call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"}],"doi":"10.1126/science.aad0512","oa":1,"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. ","date_created":"2018-12-11T11:52:57Z","title":"Polysialylation controls dendritic cell trafficking by regulating chemokine recognition","oa_version":"Submitted Version","publication_status":"published","publist_id":"5570"}]