[{"publication":"Frontiers in Immunology","status":"public","ddc":["570"],"citation":{"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>.","short":"K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology 12 (2021).","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.","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.","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>.","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>","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>"},"article_number":"630002","ec_funded":1,"scopus_import":"1","has_accepted_license":"1","publisher":"Frontiers","file":[{"content_type":"application/pdf","file_size":3740146,"checksum":"663f5a48375e42afa4bfef58d42ec186","access_level":"open_access","date_updated":"2021-03-22T12:08:26Z","date_created":"2021-03-22T12:08:26Z","success":1,"file_name":"2021_FrontiersImmumo_Vaahtomeri.pdf","creator":"dernst","file_id":"9277","relation":"main_file"}],"date_updated":"2025-04-14T07:42:07Z","year":"2021","author":[{"orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","first_name":"Kari","last_name":"Vaahtomeri"},{"full_name":"Moussion, Christine","last_name":"Moussion","first_name":"Christine","id":"3356F664-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"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"quality_controlled":"1","article_type":"original","oa":1,"volume":12,"day":"25","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_status":"published","intvolume":"        12","pmid":1,"language":[{"iso":"eng"}],"date_published":"2021-02-25T00:00:00Z","isi":1,"_id":"9259","publication_identifier":{"eissn":["1664-3224"]},"corr_author":"1","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.","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."}],"file_date_updated":"2021-03-22T12:08:26Z","type":"journal_article","month":"02","project":[{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients"},{"call_identifier":"FWF","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"external_id":{"pmid":["33717158"],"isi":["000627134400001"]},"title":"Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium","article_processing_charge":"No","oa_version":"Published Version","date_created":"2021-03-21T23:01:20Z","doi":"10.3389/fimmu.2021.630002","department":[{"_id":"MiSi"},{"_id":"Bio"}]},{"article_type":"original","quality_controlled":"1","oa":1,"volume":351,"issue":"6269","day":"08","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","publication":"Science","status":"public","page":"186 - 190","citation":{"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>","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>","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.","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.","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>.","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."},"publisher":"American Association for the Advancement of Science","ec_funded":1,"scopus_import":"1","date_updated":"2025-09-18T11:01:30Z","acknowledged_ssus":[{"_id":"SSU"}],"author":[{"orcid":"0000-0001-6165-5738","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","full_name":"Kiermaier, Eva","first_name":"Eva","last_name":"Kiermaier"},{"id":"3356F664-F248-11E8-B48F-1D18A9856A87","full_name":"Moussion, Christine","last_name":"Moussion","first_name":"Christine"},{"full_name":"Veldkamp, Christopher","first_name":"Christopher","last_name":"Veldkamp"},{"full_name":"Gerardy  Schahn, Rita","first_name":"Rita","last_name":"Gerardy  Schahn"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid"},{"full_name":"Williams, Larry","first_name":"Larry","last_name":"Williams"},{"full_name":"Chaffee, Gary","first_name":"Gary","last_name":"Chaffee"},{"full_name":"Phillips, Andrew","last_name":"Phillips","first_name":"Andrew"},{"full_name":"Freiberger, Friedrich","last_name":"Freiberger","first_name":"Friedrich"},{"full_name":"Imre, Richard","first_name":"Richard","last_name":"Imre"},{"first_name":"Deni","last_name":"Taleski","full_name":"Taleski, Deni"},{"full_name":"Payne, Richard","last_name":"Payne","first_name":"Richard"},{"first_name":"Asolina","last_name":"Braun","full_name":"Braun, Asolina"},{"first_name":"Reinhold","last_name":"Förster","full_name":"Förster, Reinhold"},{"full_name":"Mechtler, Karl","last_name":"Mechtler","first_name":"Karl"},{"first_name":"Martina","last_name":"Mühlenhoff","full_name":"Mühlenhoff, Martina"},{"full_name":"Volkman, Brian","first_name":"Brian","last_name":"Volkman"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"}],"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. ","corr_author":"1","month":"01","type":"journal_article","abstract":[{"text":"The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.\r\n","lang":"eng"}],"external_id":{"isi":["000367806500045"],"pmid":["26657283"]},"project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7"},{"grant_number":"289720","name":"Stromal Cell-immune Cell Interactions in Health and Disease","_id":"25A76F58-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"call_identifier":"FWF","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"title":"Polysialylation controls dendritic cell trafficking by regulating chemokine recognition","date_created":"2018-12-11T11:52:57Z","oa_version":"Submitted Version","doi":"10.1126/science.aad0512","article_processing_charge":"No","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/","open_access":"1"}],"department":[{"_id":"MiSi"}],"intvolume":"       351","publication_status":"published","publist_id":"5570","pmid":1,"language":[{"iso":"eng"}],"date_published":"2016-01-08T00:00:00Z","isi":1,"_id":"1599"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"quality_controlled":"1","oa":1,"volume":9,"issue":"1","day":"22","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","status":"public","publication":"PLoS One","citation":{"ieee":"L. Stoler Barak, C. Moussion, E. Shezen, M. Hatzav, M. K. Sixt, and R. Alon, “Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects,” <i>PLoS One</i>, vol. 9, no. 1. Public Library of Science, 2014.","mla":"Stoler Barak, Liat, et al. “Blood Vessels Pattern Heparan Sulfate Gradients between Their Apical and Basolateral Aspects.” <i>PLoS One</i>, vol. 9, no. 1, e85699, Public Library of Science, 2014, doi:<a href=\"https://doi.org/10.1371/journal.pone.0085699\">10.1371/journal.pone.0085699</a>.","apa":"Stoler Barak, L., Moussion, C., Shezen, E., Hatzav, M., Sixt, M. K., &#38; Alon, R. (2014). Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects. <i>PLoS One</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0085699\">https://doi.org/10.1371/journal.pone.0085699</a>","ama":"Stoler Barak L, Moussion C, Shezen E, Hatzav M, Sixt MK, Alon R. Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects. <i>PLoS One</i>. 2014;9(1). doi:<a href=\"https://doi.org/10.1371/journal.pone.0085699\">10.1371/journal.pone.0085699</a>","chicago":"Stoler Barak, Liat, Christine Moussion, Elias Shezen, Miki Hatzav, Michael K Sixt, and Ronen Alon. “Blood Vessels Pattern Heparan Sulfate Gradients between Their Apical and Basolateral Aspects.” <i>PLoS One</i>. Public Library of Science, 2014. <a href=\"https://doi.org/10.1371/journal.pone.0085699\">https://doi.org/10.1371/journal.pone.0085699</a>.","ista":"Stoler Barak L, Moussion C, Shezen E, Hatzav M, Sixt MK, Alon R. 2014. Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects. PLoS One. 9(1), e85699.","short":"L. Stoler Barak, C. Moussion, E. Shezen, M. Hatzav, M.K. Sixt, R. Alon, PLoS One 9 (2014)."},"ddc":["570"],"article_number":"e85699","has_accepted_license":"1","scopus_import":"1","ec_funded":1,"file":[{"date_updated":"2020-07-14T12:45:33Z","access_level":"open_access","date_created":"2018-12-12T10:07:48Z","content_type":"application/pdf","file_size":12634775,"checksum":"84a8033bda2e07e39405f5acc85f4eca","creator":"system","file_name":"IST-2016-433-v1+1_journal.pone.0085699.pdf","relation":"main_file","file_id":"4646"}],"publisher":"Public Library of Science","date_updated":"2025-09-29T11:30:42Z","year":"2014","author":[{"full_name":"Stoler Barak, Liat","first_name":"Liat","last_name":"Stoler Barak"},{"full_name":"Moussion, Christine","first_name":"Christine","last_name":"Moussion","id":"3356F664-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Shezen, Elias","last_name":"Shezen","first_name":"Elias"},{"full_name":"Hatzav, Miki","last_name":"Hatzav","first_name":"Miki"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"},{"full_name":"Alon, Ronen","last_name":"Alon","first_name":"Ronen"}],"pubrep_id":"433","acknowledgement":"Michael Sixt's research is supported by the European Research Council (ERC Starting grant).","abstract":[{"lang":"eng","text":"A hallmark of immune cell trafficking is directional guidance via gradients of soluble or surface bound chemokines. Vascular endothelial cells produce, transport and deposit either their own chemokines or chemokines produced by the underlying stroma. Endothelial heparan sulfate (HS) was suggested to be a critical scaffold for these chemokine pools, but it is unclear how steep chemokine gradients are sustained between the lumenal and ablumenal aspects of blood vessels. Addressing this question by semi-quantitative immunostaining of HS moieties around blood vessels with a pan anti-HS IgM mAb, we found a striking HS enrichment in the basal lamina of resting and inflamed post capillary skin venules, as well as in high endothelial venules (HEVs) of lymph nodes. Staining of skin vessels with a glycocalyx probe further suggested that their lumenal glycocalyx contains much lower HS density than their basolateral extracellular matrix (ECM). This polarized HS pattern was observed also in isolated resting and inflamed microvascular dermal cells. Notably, progressive skin inflammation resulted in massive ECM deposition and in further HS enrichment around skin post capillary venules and their associated pericytes. Inflammation-dependent HS enrichment was not compromised in mice deficient in the main HS degrading enzyme, heparanase. Our results suggest that the blood vasculature patterns steep gradients of HS scaffolds between their lumenal and basolateral endothelial aspects, and that inflammatory processes can further enrich the HS content nearby inflamed vessels. We propose that chemokine gradients between the lumenal and ablumenal sides of vessels could be favored by these sharp HS scaffold gradients."}],"month":"01","type":"journal_article","file_date_updated":"2020-07-14T12:45:33Z","project":[{"call_identifier":"FP7","name":"Stromal Cell-immune Cell Interactions in Health and Disease","grant_number":"289720","_id":"25A76F58-B435-11E9-9278-68D0E5697425"}],"external_id":{"isi":["000330283100061"]},"title":"Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects","article_processing_charge":"No","oa_version":"Published Version","doi":"10.1371/journal.pone.0085699","date_created":"2018-12-11T11:56:22Z","department":[{"_id":"MiSi"}],"publication_status":"published","intvolume":"         9","publist_id":"4756","language":[{"iso":"eng"}],"date_published":"2014-01-22T00:00:00Z","isi":1,"_id":"2214"},{"publication":"Immunity","status":"public","citation":{"short":"C. Moussion, M.K. Sixt, Immunity 38 (2013) 853–854.","ista":"Moussion C, Sixt MK. 2013. A conduit to amplify innate immunity. Immunity. 38(5), 853–854.","chicago":"Moussion, Christine, and Michael K Sixt. “A Conduit to Amplify Innate Immunity.” <i>Immunity</i>. Cell Press, 2013. <a href=\"https://doi.org/10.1016/j.immuni.2013.05.005\">https://doi.org/10.1016/j.immuni.2013.05.005</a>.","ieee":"C. Moussion and M. K. Sixt, “A conduit to amplify innate immunity,” <i>Immunity</i>, vol. 38, no. 5. Cell Press, pp. 853–854, 2013.","mla":"Moussion, Christine, and Michael K. Sixt. “A Conduit to Amplify Innate Immunity.” <i>Immunity</i>, vol. 38, no. 5, Cell Press, 2013, pp. 853–54, doi:<a href=\"https://doi.org/10.1016/j.immuni.2013.05.005\">10.1016/j.immuni.2013.05.005</a>.","apa":"Moussion, C., &#38; Sixt, M. K. (2013). A conduit to amplify innate immunity. <i>Immunity</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.immuni.2013.05.005\">https://doi.org/10.1016/j.immuni.2013.05.005</a>","ama":"Moussion C, Sixt MK. A conduit to amplify innate immunity. <i>Immunity</i>. 2013;38(5):853-854. doi:<a href=\"https://doi.org/10.1016/j.immuni.2013.05.005\">10.1016/j.immuni.2013.05.005</a>"},"page":"853 - 854","publisher":"Cell Press","scopus_import":"1","date_updated":"2025-09-29T13:51:00Z","author":[{"id":"3356F664-F248-11E8-B48F-1D18A9856A87","full_name":"Moussion, Christine","last_name":"Moussion","first_name":"Christine"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"year":"2013","quality_controlled":"1","volume":38,"issue":"5","day":"23","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","intvolume":"        38","publication_status":"published","publist_id":"3969","language":[{"iso":"eng"}],"date_published":"2013-05-23T00:00:00Z","_id":"2830","isi":1,"corr_author":"1","month":"05","type":"journal_article","external_id":{"isi":["000330942500005"]},"title":"A conduit to amplify innate immunity","doi":"10.1016/j.immuni.2013.05.005","oa_version":"None","date_created":"2018-12-11T11:59:49Z","article_processing_charge":"No","department":[{"_id":"MiSi"}]},{"publisher":"American Association for the Advancement of Science","ec_funded":1,"scopus_import":"1","page":"328 - 332","citation":{"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. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.1228456\">https://doi.org/10.1126/science.1228456</a>","ama":"Weber M, Hauschild R, Schwarz J, et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. <i>Science</i>. 2013;339(6117):328-332. doi:<a href=\"https://doi.org/10.1126/science.1228456\">10.1126/science.1228456</a>","mla":"Weber, Michele, et al. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” <i>Science</i>, vol. 339, no. 6117, American Association for the Advancement of Science, 2013, pp. 328–32, doi:<a href=\"https://doi.org/10.1126/science.1228456\">10.1126/science.1228456</a>.","ieee":"M. Weber <i>et al.</i>, “Interstitial dendritic cell guidance by haptotactic chemokine gradients,” <i>Science</i>, vol. 339, no. 6117. American Association for the Advancement of Science, pp. 328–332, 2013.","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.","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.","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.” <i>Science</i>. American Association for the Advancement of Science, 2013. <a href=\"https://doi.org/10.1126/science.1228456\">https://doi.org/10.1126/science.1228456</a>."},"publication":"Science","status":"public","author":[{"id":"3A3FC708-F248-11E8-B48F-1D18A9856A87","full_name":"Weber, Michele","first_name":"Michele","last_name":"Weber"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","first_name":"Jan","last_name":"Schwarz"},{"id":"3356F664-F248-11E8-B48F-1D18A9856A87","last_name":"Moussion","first_name":"Christine","full_name":"Moussion, Christine"},{"last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Legler, Daniel","first_name":"Daniel","last_name":"Legler"},{"full_name":"Luther, Sanjiv","last_name":"Luther","first_name":"Sanjiv"},{"full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","first_name":"Mark Tobias","orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"year":"2013","date_updated":"2025-09-29T13:45:52Z","oa":1,"article_type":"original","quality_controlled":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","day":"18","issue":"6117","volume":339,"language":[{"iso":"eng"}],"publist_id":"3959","intvolume":"       339","publication_status":"published","isi":1,"_id":"2839","date_published":"2013-01-18T00:00:00Z","external_id":{"isi":["000313622000047"]},"project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556"},{"name":"Cell migration in complex environments: from in vivo experiments to theoretical models","grant_number":"RGP0058/2011","_id":"25ABD200-B435-11E9-9278-68D0E5697425"}],"type":"journal_article","month":"01","abstract":[{"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.","lang":"eng"}],"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.).","corr_author":"1","department":[{"_id":"MiSi"},{"_id":"Bio"}],"doi":"10.1126/science.1228456","date_created":"2018-12-11T11:59:52Z","oa_version":"Published Version","article_processing_charge":"No","main_file_link":[{"url":"https://kops.uni-konstanz.de/bitstream/123456789/26341/2/Weber_263418.pdf","open_access":"1"}],"title":"Interstitial dendritic cell guidance by haptotactic chemokine gradients"},{"scopus_import":"1","publisher":"Nature Publishing Group","publication":"Nature Reviews Immunology","status":"public","page":"762 - 773","citation":{"ieee":"J. Girard, C. Moussion, and R. Förster, “HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes,” <i>Nature Reviews Immunology</i>, vol. 12, no. 11. Nature Publishing Group, pp. 762–773, 2012.","mla":"Girard, Jean, et al. “HEVs, Lymphatics and Homeostatic Immune Cell Trafficking in Lymph Nodes.” <i>Nature Reviews Immunology</i>, vol. 12, no. 11, Nature Publishing Group, 2012, pp. 762–73, doi:<a href=\"https://doi.org/10.1038/nri3298\">10.1038/nri3298</a>.","ama":"Girard J, Moussion C, Förster R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. <i>Nature Reviews Immunology</i>. 2012;12(11):762-773. doi:<a href=\"https://doi.org/10.1038/nri3298\">10.1038/nri3298</a>","apa":"Girard, J., Moussion, C., &#38; Förster, R. (2012). HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. <i>Nature Reviews Immunology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/nri3298\">https://doi.org/10.1038/nri3298</a>","chicago":"Girard, Jean, Christine Moussion, and Reinhold Förster. “HEVs, Lymphatics and Homeostatic Immune Cell Trafficking in Lymph Nodes.” <i>Nature Reviews Immunology</i>. Nature Publishing Group, 2012. <a href=\"https://doi.org/10.1038/nri3298\">https://doi.org/10.1038/nri3298</a>.","short":"J. Girard, C. Moussion, R. Förster, Nature Reviews Immunology 12 (2012) 762–773.","ista":"Girard J, Moussion C, Förster R. 2012. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nature Reviews Immunology. 12(11), 762–773."},"year":"2012","author":[{"first_name":"Jean","last_name":"Girard","full_name":"Girard, Jean"},{"id":"3356F664-F248-11E8-B48F-1D18A9856A87","first_name":"Christine","last_name":"Moussion","full_name":"Moussion, Christine"},{"last_name":"Förster","first_name":"Reinhold","full_name":"Förster, Reinhold"}],"date_updated":"2025-09-30T08:12:46Z","quality_controlled":"1","day":"01","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","volume":12,"issue":"11","language":[{"iso":"eng"}],"publication_status":"published","intvolume":"        12","publist_id":"3787","_id":"2945","isi":1,"date_published":"2012-11-01T00:00:00Z","abstract":[{"lang":"eng","text":"In search of foreign antigens, lymphocytes recirculate from the blood, through lymph nodes, into lymphatics and back to the blood. Dendritic cells also migrate to lymph nodes for optimal interaction with lymphocytes. This continuous trafficking of immune cells into and out of lymph nodes is essential for immune surveillance of foreign invaders. In this article, we review our current understanding of the functions of high endothelial venules (HEVs), stroma and lymphatics in the entry, positioning and exit of immune cells in lymph nodes during homeostasis, and we highlight the unexpected role of dendritic cells in the control of lymphocyte homing through HEVs."}],"type":"journal_article","month":"11","external_id":{"isi":["000310523400010"]},"acknowledgement":"We thank M. Sixt and A. Peixoto for helpful comments on the manuscript. Work in the laboratory of J.-P.G. is supported by grants from Fondation ARC pour la Recherche sur le Cancer, Agence Nationale de la Recherche (ANR), Institut National du Cancer (INCA), Fondation RITC and Région Midi-Pyrénées. Research by R.F. is supported by Deutsche Forschungsgemeinschaft (DFG) grants SFB621-A1, SFB738-B5, SFB587-B3, SFB900-B1 and KFO 250-FO 334/2-1. We regret that, owing to space limitations, we could not always quote the work of colleagues who have contributed to the field.","department":[{"_id":"MiSi"}],"title":"HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes","article_processing_charge":"No","doi":"10.1038/nri3298","date_created":"2018-12-11T12:00:29Z","oa_version":"None"}]