--- _id: '1599' 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" acknowledged_ssus: - _id: SSU 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. ' article_processing_charge: No article_type: original author: - first_name: Eva full_name: Kiermaier, Eva id: 3EB04B78-F248-11E8-B48F-1D18A9856A87 last_name: Kiermaier orcid: 0000-0001-6165-5738 - first_name: Christine full_name: Moussion, Christine id: 3356F664-F248-11E8-B48F-1D18A9856A87 last_name: Moussion - first_name: Christopher full_name: Veldkamp, Christopher last_name: Veldkamp - first_name: Rita full_name: Gerardy Schahn, Rita last_name: Gerardy Schahn - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Larry full_name: Williams, Larry last_name: Williams - first_name: Gary full_name: Chaffee, Gary last_name: Chaffee - first_name: Andrew full_name: Phillips, Andrew last_name: Phillips - first_name: Friedrich full_name: Freiberger, Friedrich last_name: Freiberger - first_name: Richard full_name: Imre, Richard last_name: Imre - first_name: Deni full_name: Taleski, Deni last_name: Taleski - first_name: Richard full_name: Payne, Richard last_name: Payne - first_name: Asolina full_name: Braun, Asolina last_name: Braun - first_name: Reinhold full_name: Förster, Reinhold last_name: Förster - first_name: Karl full_name: Mechtler, Karl last_name: Mechtler - first_name: Martina full_name: Mühlenhoff, Martina last_name: Mühlenhoff - first_name: Brian full_name: Volkman, Brian last_name: Volkman - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Kiermaier E, Moussion C, Veldkamp C, et al. Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. 2016;351(6269):186-190. doi:10.1126/science.aad0512 apa: Kiermaier, E., Moussion, C., Veldkamp, C., Gerardy  Schahn, R., de Vries, I., Williams, L., … Sixt, M. K. (2016). Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aad0512 chicago: Kiermaier, Eva, Christine Moussion, Christopher Veldkamp, Rita Gerardy  Schahn, Ingrid de Vries, Larry Williams, Gary Chaffee, et al. “Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aad0512. ieee: E. Kiermaier et al., “Polysialylation controls dendritic cell trafficking by regulating chemokine recognition,” Science, vol. 351, no. 6269. American Association for the Advancement of Science, pp. 186–190, 2016. ista: Kiermaier E, Moussion C, Veldkamp C, Gerardy  Schahn R, de Vries I, Williams L, Chaffee G, Phillips A, Freiberger F, Imre R, Taleski D, Payne R, Braun A, Förster R, Mechtler K, Mühlenhoff M, Volkman B, Sixt MK. 2016. Polysialylation controls dendritic cell trafficking by regulating chemokine recognition. Science. 351(6269), 186–190. mla: Kiermaier, Eva, et al. “Polysialylation Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science, vol. 351, no. 6269, American Association for the Advancement of Science, 2016, pp. 186–90, doi:10.1126/science.aad0512. 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. date_created: 2018-12-11T11:52:57Z date_published: 2016-01-08T00:00:00Z date_updated: 2021-01-12T06:51:52Z day: '08' department: - _id: MiSi doi: 10.1126/science.aad0512 ec_funded: 1 external_id: pmid: - '26657283' intvolume: ' 351' issue: '6269' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/ month: '01' oa: 1 oa_version: Submitted Version page: 186 - 190 pmid: 1 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) - _id: 25A76F58-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '289720' name: Stromal Cell-immune Cell Interactions in Health and Disease - _id: 25A8E5EA-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Y 564-B12 name: Cytoskeletal force generation and transduction of leukocytes (FWF) publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '5570' quality_controlled: '1' scopus_import: 1 status: public title: Polysialylation controls dendritic cell trafficking by regulating chemokine recognition type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 351 year: '2016' ... --- _id: '2214' 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. acknowledgement: Michael Sixt's research is supported by the European Research Council (ERC Starting grant). article_number: e85699 author: - first_name: Liat full_name: Stoler Barak, Liat last_name: Stoler Barak - first_name: Christine full_name: Moussion, Christine id: 3356F664-F248-11E8-B48F-1D18A9856A87 last_name: Moussion - first_name: Elias full_name: Shezen, Elias last_name: Shezen - first_name: Miki full_name: Hatzav, Miki last_name: Hatzav - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 - first_name: Ronen full_name: Alon, Ronen last_name: Alon 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. PLoS One. 2014;9(1). doi:10.1371/journal.pone.0085699 apa: Stoler Barak, L., Moussion, C., Shezen, E., Hatzav, M., Sixt, M. K., & Alon, R. (2014). Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0085699 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.” PLoS One. Public Library of Science, 2014. https://doi.org/10.1371/journal.pone.0085699. 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,” PLoS One, vol. 9, no. 1. Public Library of Science, 2014. 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. mla: Stoler Barak, Liat, et al. “Blood Vessels Pattern Heparan Sulfate Gradients between Their Apical and Basolateral Aspects.” PLoS One, vol. 9, no. 1, e85699, Public Library of Science, 2014, doi:10.1371/journal.pone.0085699. short: L. Stoler Barak, C. Moussion, E. Shezen, M. Hatzav, M.K. Sixt, R. Alon, PLoS One 9 (2014). date_created: 2018-12-11T11:56:22Z date_published: 2014-01-22T00:00:00Z date_updated: 2021-01-12T06:56:03Z day: '22' ddc: - '570' department: - _id: MiSi doi: 10.1371/journal.pone.0085699 ec_funded: 1 file: - access_level: open_access checksum: 84a8033bda2e07e39405f5acc85f4eca content_type: application/pdf creator: system date_created: 2018-12-12T10:07:48Z date_updated: 2020-07-14T12:45:33Z file_id: '4646' file_name: IST-2016-433-v1+1_journal.pone.0085699.pdf file_size: 12634775 relation: main_file file_date_updated: 2020-07-14T12:45:33Z has_accepted_license: '1' intvolume: ' 9' issue: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '01' oa: 1 oa_version: Published Version project: - _id: 25A76F58-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '289720' name: Stromal Cell-immune Cell Interactions in Health and Disease publication: PLoS One publication_status: published publisher: Public Library of Science publist_id: '4756' pubrep_id: '433' quality_controlled: '1' scopus_import: 1 status: public title: Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects tmp: 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) short: CC BY (4.0) type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 9 year: '2014' ...