{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:00:53Z","timestamp":1790240453896,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL163570\u201001A1"],"award-info":[{"award-number":["R01HL163570\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Barrier Immunity"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    RNA sequencing (RNA\u2010seq) analysis revealed transcriptional features indicative of sustained immunosuppression within regulatory T cells (Tregs) isolated from atherosclerotic tissues, highlighting the critical contribution of immune checkpoint (ICP) receptor\u2013ligand interactions to atherosclerosis progression. To comprehensively characterize the roles of ICP signaling in this context, we integrated transcriptomic profiling, quantitative RT\u2010PCR, and flow cytometry analysis, yielding several key findings: (1) Multiomics integration revealed global transcriptomic alterations in ICP receptors and ligands across diverse tissues, immune cell types, and disease stages in both human and murine models of atherosclerosis; (2) Several ICP components demonstrated functional relevance, including dual\u2010function ligand CD155 (PVR); inhibitory ligands Lgals3 and Itgb1; stimulatory ligands Tnfrsf9 and CD48; and inhibitory receptors Havcr2 and Lair1. These molecules act as microenvironmental sensors, dynamically responding to atherosclerotic cues; (3) Experimental validation confirmed upregulation of the CD155\u2010TIGIT axis within immune cells of atherosclerotic plaques. Notably, CD155 expression positively correlated with CD206 expression in both CD11b\n                    <jats:sup>+<\/jats:sup>\n                    CD11c\n                    <jats:sup>+<\/jats:sup>\n                    and CD11b\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD11c\n                    <jats:sup>+<\/jats:sup>\n                    cells, irrespective of tissue context; and (4) The CD206\n                    <jats:sup>+<\/jats:sup>\n                    macrophages\/DCs\u2013CD155\u2013TIGIT\n                    <jats:sup>+<\/jats:sup>\n                    Treg axis emerged as a potential ICP\u2010mediated pathway that confers immunoregulatory protection against atherosclerosis progression. Collectively, these findings uncover novel immunomodulatory roles for ICP ligands in atherosclerosis, expanding their known functions beyond adaptive immune regulation to include modulation of innate immune responses within atherosclerotic lesions.\n                  <\/jats:p>","DOI":"10.1002\/dni2.70016","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:54:12Z","timestamp":1789664052000},"page":"131-146","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Omics Analysis Reveals a CD206\n                    <sup>+<\/sup>\n                    Macrophage\/Dendritic Cell\u2013CD155\u2013TIGIT\n                    <sup>+<\/sup>\n                    Regulatory T Cell Axis as a Protective Immune Checkpoint Pathway in Atherosclerosis Progression"],"prefix":"10.1002","volume":"2","author":[{"given":"Ying","family":"Shao","sequence":"first","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5807-3390","authenticated-orcid":false,"given":"Fatma","family":"Saaoud","sequence":"additional","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Ben Issa","sequence":"additional","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keman","family":"Xu","sequence":"additional","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Lu","sequence":"additional","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Yu","family":"Hung","sequence":"additional","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yuan","sequence":"additional","affiliation":[{"name":"Lemole Center for Integrated Lymphatics and Vascular Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juncheng","family":"Wei","sequence":"additional","affiliation":[{"name":"Centers for Metabolic Disease Research and Thrombosis Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Centers for Metabolic Disease Research and Thrombosis Research  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Mohsin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences Aging+ Cardiovascular Discovery Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8329-6086","authenticated-orcid":false,"given":"Zhengjie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Translational and Clinical Lung Research Lewis Katz School of Medicine Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Kosmider","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Translational and Clinical Lung Research Lewis Katz School of Medicine Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-8761","authenticated-orcid":false,"given":"Laisel","family":"Martinez","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery Leonard M. 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