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Here, we found that leukocytes had the glycocalyx component heparan sulfate on their cell surface and that it was lost in response to psoriasis-like skin inflammation. In contrast, endothelial heparan sulfate was not affected. Treatment with a heparan sulfate mimetic during psoriasis-like skin inflammation in mice protected heparan sulfate from cleavage by myeloid cell\u2013derived heparanase and resulted in reduced leukocyte accumulation in the skin. However, clinical signs of inflammation were increased because of the reduced numbers of T regulatory cells that were recruited. These findings refine our understanding of immune cell recruitment by revealing the presence and function of a heparan sulfate glycocalyx on immune cells and highlight the complex effects of heparanase inhibitors on the immune response in this context.<\/jats:p>","DOI":"10.1126\/scisignal.adr0011","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:58:17Z","timestamp":1762282697000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7805-2503","authenticated-orcid":true,"given":"Megan J.","family":"Priestley","sequence":"first","affiliation":[{"name":"Manchester Cell-Matrix Centre, Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK."},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Boston, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3475-6555","authenticated-orcid":true,"given":"Anna K.","family":"Hains","sequence":"additional","affiliation":[{"name":"Manchester Cell-Matrix Centre, Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-9153","authenticated-orcid":true,"given":"Iashia Z.","family":"Mulholland","sequence":"additional","affiliation":[{"name":"Manchester Cell-Matrix Centre, Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0606-3533","authenticated-orcid":true,"given":"Sam","family":"Spijkers-Shaw","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA."},{"name":"Ferrier Research Institute, Victoria University of Wellington, Gracefield Research Centre, Lower Hutt 5046, New Zealand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8340-8727","authenticated-orcid":true,"given":"Joshua C.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Laboratory for Intravital Imaging and Dynamics of Tumor Progression, VIB Center for Cancer Biology, Leuven 3000, Belgium."},{"name":"Intravital Imaging Expertise Center, VIB Center for Cancer Biology, Leuven 3000, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3552-1274","authenticated-orcid":true,"given":"Gareth","family":"Howell","sequence":"additional","affiliation":[{"name":"Flow Cytometry Technology Platform, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7626-481X","authenticated-orcid":true,"given":"Amanda J. 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