{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:28:37Z","timestamp":1792553317710,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Patients with spondyloarthritis (SpA) often present with microscopic signs of gut inflammation, a risk factor for progressive disease. We investigated whether mucosal innate\u2010like T cells are involved in dysregulated interleukin\u201023 (IL\u201023)\/IL\u201017 responses in the gut\u2010joint axis in SpA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ileal and colonic intraepithelial lymphocytes (IELs), lamina propria lymphocytes (LPLs), and paired peripheral blood mononuclear cells (PBMCs) were isolated from treatment\u2010naive patients with nonradiographic axial SpA with (n\u00a0=\u00a011) and without (n\u00a0=\u00a014) microscopic gut inflammation and healthy controls (n\u00a0=\u00a015) undergoing ileocolonoscopy. The presence of gut inflammation was assessed histopathologically. Immunophenotyping of innate\u2010like T cells and conventional T cells was performed using intracellular flow cytometry. Unsupervised clustering analysis was done by FlowSOM technology. Serum IL\u201017A levels were measured via Luminex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Microscopic gut inflammation in nonradiographic axial SpA was characterized by increased ileal intraepithelial \u03b3\u03b4\u2010hi T cells, a \u03b3\u03b4\u2010T cell subset with elevated \u03b3\u03b4\u2010T cell receptor expression. \u03b3\u03b4\u2010hi T cells\u00a0were also increased in PBMCs of patients with nonradiographic axial SpA versus healthy controls and were strongly associated with Ankylosing Spondylitis Disease Activity Score. The abundance of mucosal\u2010associated invariant T cells and invariant natural killer T cells was unaltered. Innate\u2010like T cells in the inflamed gut showed increased ROR\u03b3t, IL\u201017A, and IL\u201022 levels with loss of T\u2010bet, a signature that was less pronounced in conventional T cells. Presence of gut inflammation was associated with higher serum IL\u201017A levels. In patients treated with tumor necrosis factor blockade, the proportion of \u03b3\u03b4\u2010hi cells and ROR\u03b3t expression in blood was completely restored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intestinal innate\u2010like T cells display marked type 17 skewing in the inflamed gut mucosa of patients with nonradiographic axial SpA. \u03b3\u03b4\u2010hi T cells are linked to intestinal inflammation and disease activity in SpA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42627","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T05:56:01Z","timestamp":1686290161000},"page":"1969-1982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Gut Inflammation in Axial Spondyloarthritis Patients is Characterized by a Marked Type 17 Skewed Mucosal Innate\u2010like T Cell Signature"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-8109","authenticated-orcid":false,"given":"C\u00e9line","family":"Mortier","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Quintelier","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium, Data Mining and Modeling for Biomedicine group, VIB\u2010UGent Center for Inflammation Research, Ghent, Belgium, and Department of Pulmonary Medicine Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7062-8934","authenticated-orcid":false,"given":"Ann\u2010Sophie","family":"De Craemer","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5503-000X","authenticated-orcid":false,"given":"Thomas","family":"Renson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7954-9044","authenticated-orcid":false,"given":"Liselotte","family":"Deroo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Dumas","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline","family":"Verheugen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Coudenys","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine","family":"Decruy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzanna","family":"Lukasik","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Van Gassen","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics, Computer Science and Statistics Ghent University and Data Mining and Modeling for Biomedicine group, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvan","family":"Saeys","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics, Computer Science and Statistics Ghent University and Data Mining and Modeling for Biomedicine group, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hoorens","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Health Sciences Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triana","family":"Lobat\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Ghent University and Department of Gastroenterology Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Faculty of Medicine and Health Sciences Ghent University and Unit for Molecular Immunology and Inflammation, VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Van de Wiele","sequence":"additional","affiliation":[{"name":"Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering Ghent University  Ghent 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