{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:47:05Z","timestamp":1791780425653,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5T32AI007405"],"award-info":[{"award-number":["5T32AI007405"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1TR002533"],"award-info":[{"award-number":["TL1TR002533"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["F31DK138543"],"award-info":[{"award-number":["F31DK138543"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012495","name":"Spondylitis Association of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012495","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"\n Objective<\/jats:title>\n \n The gut\u2013joint axis is a central paradigm in spondyloarthritis, yet the cellular mechanisms linking intestinal and joint immunity remain poorly understood. One potential link is T cell receptor \u03b1\u03b2\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n colon intraepithelial lymphocytes (cIELs) that can traffic to extraintestinal tissues, including the joint. Within an inflamed joint, trafficked cIELs display both regulatory and inflammatory capacity. We sought to determine whether this functional identity is determined by an impaired epithelium or shaped by the joint environment.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We combined colonoscopy\u2010guided photoconversion in KikGR mice with single\u2010cell multiomic profiling and flow cytometry to trace and characterize CD4\n +<\/jats:sup>\n cIELs in the spleen and joint\u2010draining lymph nodes. Intestinal perturbation was induced by dextran sodium sulfate (DSS) and epithelial\u2010specific major histocompatibility complex class II (MHCII) gene deletion.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Epithelial\u2010derived CD4\n +<\/jats:sup>\n T cells were enriched for tolerogenic phenotypes, marked by expression of CD73, FR4, and Foxp3. This phenotype persisted despite DSS\u2010induced intestinal inflammation and was independent of epithelial MHCII expression. However, single\u2010cell transcriptomic, epigenetic, and T cell receptor analyses revealed that shared clones undergo tissue\u2010specific transcriptional reprogramming to more activated states after exiting the epithelium.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings define CD4\n +<\/jats:sup>\n cIELs as mobile T cells that retain tolerogenic phenotypes with functional plasticity to a more activated state determined by extraintestinal microenvironments, indicating that the local environment of the joint\u2010draining lymph nodes, rather than the gut, is important in determining the function of gut\u2010trafficked CD4\n +<\/jats:sup>\n T cells.\n <\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.70358","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:03:29Z","timestamp":1790831009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extraintestinal Reprogramming of Colon\u2010Derived\n CD4<\/scp>\n +<\/sup>\n Intraepithelial Lymphocytes Reveals a Mechanism Underlying the Gut\u2013Joint Axis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1512-882X","authenticated-orcid":false,"given":"Sarah M.","family":"Danielson","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of Colorado Anschutz Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Eck","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of Colorado Anschutz Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucai","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of Colorado Anschutz Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Helena","family":"Jonsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of Colorado Anschutz Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-4195","authenticated-orcid":false,"given":"Kristine A.","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of Colorado Anschutz 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