{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:03:12Z","timestamp":1784264592849,"version":"3.55.0"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Crohn\u2019s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. <jats:italic>CD5<\/jats:italic> and <jats:italic>CD6<\/jats:italic> are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While <jats:italic>CD5<\/jats:italic> and <jats:italic>CD6<\/jats:italic> expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, <jats:italic>Cd5<\/jats:italic>- and <jats:italic>Cd6<\/jats:italic>-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting <jats:italic>Cd5<\/jats:italic> and <jats:italic>Cd6<\/jats:italic> expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of <jats:italic>CD5<\/jats:italic> (rs2241002 and rs2229177) and <jats:italic>CD6<\/jats:italic> (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of <jats:italic>CD5<\/jats:italic> variation with CD ileal location (rs2241002<jats:sup>CC<\/jats:sup>) and requirement of biological therapies (rs2241002<jats:sup>C<\/jats:sup>-rs2229177<jats:sup>T<\/jats:sup> haplotype), and with poor UC prognosis (rs2241002<jats:sup>T<\/jats:sup>-rs2229177<jats:sup>T<\/jats:sup> haplotype). Regarding <jats:italic>CD6<\/jats:italic>, association was observed with CD ileal location (rs17824933<jats:sup>G<\/jats:sup>) and poor prognosis (rs12360861<jats:sup>G<\/jats:sup>), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933<jats:sup>G<\/jats:sup>). The present experimental and genetic evidence support a role for <jats:italic>CD5<\/jats:italic> and <jats:italic>CD6<\/jats:italic> expression and variation in IBD\u2019s clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.<\/jats:p>","DOI":"10.3389\/fimmu.2022.966184","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T08:01:45Z","timestamp":1663747305000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Sergi","family":"Casad\u00f3-Llombart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Velasco-de Andr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Catal\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Leyton-Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Guti\u00e9rrez-C\u00f3zar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Su\u00e1rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelia","family":"Armiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Carreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Esteller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ricart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Ord\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier P.","family":"Gisbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Chaparro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Esteve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"M\u00e1rquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Busquets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Iglesias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Garc\u00eda-Planella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Mart\u00edn-Arranz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Lohmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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