[{"publication":"Science","acknowledged_ssus":[{"_id":"SSU"}],"oa_version":"Submitted Version","project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"},{"grant_number":"289720","name":"Stromal Cell-immune Cell Interactions in Health and Disease","_id":"25A76F58-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)"}],"month":"01","language":[{"iso":"eng"}],"date_published":"2016-01-08T00:00:00Z","type":"journal_article","oa":1,"publist_id":"5570","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/","open_access":"1"}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1599","pmid":1,"scopus_import":1,"author":[{"full_name":"Kiermaier, Eva","orcid":"0000-0001-6165-5738","last_name":"Kiermaier","first_name":"Eva","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christine","last_name":"Moussion","full_name":"Moussion, Christine","id":"3356F664-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Veldkamp, Christopher","last_name":"Veldkamp","first_name":"Christopher"},{"first_name":"Rita","last_name":"Gerardy  Schahn","full_name":"Gerardy  Schahn, Rita"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid","first_name":"Ingrid","last_name":"De Vries"},{"full_name":"Williams, Larry","first_name":"Larry","last_name":"Williams"},{"full_name":"Chaffee, Gary","last_name":"Chaffee","first_name":"Gary"},{"last_name":"Phillips","first_name":"Andrew","full_name":"Phillips, Andrew"},{"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"},{"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"},{"first_name":"Karl","last_name":"Mechtler","full_name":"Mechtler, Karl"},{"last_name":"Mühlenhoff","first_name":"Martina","full_name":"Mühlenhoff, Martina"},{"full_name":"Volkman, Brian","last_name":"Volkman","first_name":"Brian"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"issue":"6269","publication_status":"published","date_created":"2018-12-11T11:52:57Z","department":[{"_id":"MiSi"}],"article_processing_charge":"No","title":"Polysialylation controls dendritic cell trafficking by regulating chemokine recognition","intvolume":"       351","page":"186 - 190","quality_controlled":"1","ec_funded":1,"publisher":"American Association for the Advancement of Science","article_type":"original","date_updated":"2021-01-12T06:51:52Z","year":"2016","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.","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>.","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.” <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>.","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."},"external_id":{"pmid":["26657283"]},"doi":"10.1126/science.aad0512","day":"08","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"}],"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. ","volume":351},{"acknowledgement":"Michael Sixt's research is supported by the European Research Council (ERC Starting grant).","volume":9,"ddc":["570"],"date_updated":"2021-01-12T06:56:03Z","year":"2014","citation":{"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>","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>","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>.","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.","short":"L. Stoler Barak, C. Moussion, E. Shezen, M. Hatzav, M.K. Sixt, R. Alon, PLoS One 9 (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>.","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."},"doi":"10.1371/journal.pone.0085699","day":"22","abstract":[{"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.","lang":"eng"}],"ec_funded":1,"quality_controlled":"1","file_date_updated":"2020-07-14T12:45:33Z","publisher":"Public Library of Science","_id":"2214","scopus_import":1,"author":[{"full_name":"Stoler Barak, Liat","first_name":"Liat","last_name":"Stoler Barak"},{"last_name":"Moussion","first_name":"Christine","full_name":"Moussion, Christine","id":"3356F664-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Shezen, Elias","first_name":"Elias","last_name":"Shezen"},{"first_name":"Miki","last_name":"Hatzav","full_name":"Hatzav, Miki"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K"},{"first_name":"Ronen","last_name":"Alon","full_name":"Alon, Ronen"}],"issue":"1","publication_status":"published","date_created":"2018-12-11T11:56:22Z","department":[{"_id":"MiSi"}],"pubrep_id":"433","title":"Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects","intvolume":"         9","file":[{"date_updated":"2020-07-14T12:45:33Z","file_name":"IST-2016-433-v1+1_journal.pone.0085699.pdf","content_type":"application/pdf","date_created":"2018-12-12T10:07:48Z","file_size":12634775,"checksum":"84a8033bda2e07e39405f5acc85f4eca","file_id":"4646","creator":"system","access_level":"open_access","relation":"main_file"}],"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2014-01-22T00:00:00Z","type":"journal_article","publist_id":"4756","oa":1,"language":[{"iso":"eng"}],"publication":"PLoS One","has_accepted_license":"1","oa_version":"Published Version","project":[{"call_identifier":"FP7","_id":"25A76F58-B435-11E9-9278-68D0E5697425","name":"Stromal Cell-immune Cell Interactions in Health and Disease","grant_number":"289720"}],"month":"01","article_number":"e85699"}]