{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:46:25Z","timestamp":1792035985020,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000222","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000222","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Dysregulated immune activation at the vascular surface drives microvascular inflammation and tissue injury in many diseases, yet current therapies do not restore immune regulation at the blood\u2010vessel interface. Terminal sialic acids engage inhibitory Siglec receptors on circulating immune cells and function as endogenous glyco\u2010immune checkpoint ligands. Loss of sialylation on vascular endothelial cells during injury disrupts this regulatory axis and promotes vascular damage. Here, we introduce a checkpoint\u2010directed glycoengineering strategy that installs multivalent Siglec\u2010engaging sialic acid ligands on a macromolecular scaffold at the vascular interface to reprogram Siglec\u2010mediated immune regulation. Covalent anchoring of Siglec\u2010engaging conjugates to the vascular surface suppressed leukocyte\u2010mediated cytotoxicity, inflammatory cytokine production, adhesion molecule accessibility, and complement deposition. Protection was dose\u2010dependent and required selective sialic acid\u2013Siglec\u20107\/\u20109 engagement, as demonstrated by enzymatic desialylation, Siglec\u2010Fc binding, and receptor blockade. In vascular allografts, this Siglec\u2010engaging modification preserved endothelial integrity and suppressed innate and adaptive immune activation, neutrophil recruitment, dendritic\u2010cell activation, and T\u2010cell infiltration. In an allogeneic rat kidney transplant model, this approach attenuated microvascular inflammation, complement deposition, and tissue injury, resulting in vascular protection and demonstrating the power of glycan reprogramming. These findings establish Siglec\u2010directed immune\u2010glycoengineering as a mechanistically defined local checkpoint strategy that reprograms the vasculature into an active immunoregulatory interface.<\/jats:p>","DOI":"10.1002\/advs.78124","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:05:10Z","timestamp":1792033510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Checkpoint\u2010Directed Glycoengineering Reprograms the Vascular Lumen for Siglec\u2010Mediated Immune Regulation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3299-6538","authenticated-orcid":false,"given":"Md Mohosin","family":"Rana","sequence":"first","affiliation":[{"name":"Centre For Blood Research Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javairia F.","family":"Rahim","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6311-9503","authenticated-orcid":false,"given":"Aaron P.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8116-9914","authenticated-orcid":false,"given":"Peyman Malek Mohammadi","family":"Nouri","sequence":"additional","affiliation":[{"name":"Centre For Blood Research Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyann","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Enns","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7354-4339","authenticated-orcid":false,"given":"Jenice M.","family":"Dumlao","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming D.","family":"Luo","sequence":"additional","affiliation":[{"name":"Centre For Blood Research Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Chemistry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Chafeeva","sequence":"additional","affiliation":[{"name":"Centre For Blood Research Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4684-9929","authenticated-orcid":false,"given":"Aizhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories Ajmera Transplant Centre Toronto General Hospital Research Institute University Health Network  Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao\u2010Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery Comprehensive Transplant Center Feinberg School of Medicine Northwestern University  Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward N.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6469-5778","authenticated-orcid":false,"given":"Zheng Jenny","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery Comprehensive Transplant Center Feinberg School of Medicine Northwestern University  Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Cypel","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories Ajmera Transplant Centre Toronto General Hospital Research Institute University Health Network  Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2063-1112","authenticated-orcid":false,"given":"Christopher","family":"Nguan","sequence":"additional","affiliation":[{"name":"Department of Urological Sciences University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4579-1048","authenticated-orcid":false,"given":"Matthew S.","family":"Macauley","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Chemistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6722-5701","authenticated-orcid":false,"given":"Stephen G.","family":"Withers","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1837-8514","authenticated-orcid":false,"given":"Jonathan C.","family":"Choy","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-7574","authenticated-orcid":false,"given":"Jayachandran N.","family":"Kizhakkedathu","sequence":"additional","affiliation":[{"name":"Centre For Blood Research Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver British Columbia Canada"},{"name":"The School of Biomedical Engineering University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010022\u201000694\u20104"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.08.019"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.ajt.2025.03.031","article-title":"Microvascular Inflammation in Kidney Allografts: New Directions for Patient Management","volume":"25","author":"B\u00f6hmig G. 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