{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:36:32Z","timestamp":1790429792424,"version":"4.1.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":75,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0902288\/1"],"award-info":[{"award-number":["G0902288\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>Defective immune regulation plays a permissive role enabling effector cells to initiate and perpetuate tissue damage, eventually resulting in autoimmune disease. Numerical and functional regulatory T\u2010cell (Treg) impairment has been previously reported in autoimmune liver disease (AILD; including autoimmune hepatitis and autoimmune sclerosing cholangitis ASC). However, in these early reports, Tregs were phenotypically defined as CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> or CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup> cells. In the current study, we reexamined phenotypic and functional properties of Tregs by adopting a more refined definition of these cells that also includes negativity or low level of expression of CD127. We studied 43 AILD patients and 22 healthy subjects (HSs) and found that CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>CD127<jats:sup>\u2212<\/jats:sup> Tregs were decreased in the former. This decrease was more marked in patients with active disease than in those in remission. In AILD, Treg frequencies correlated inversely with parameters of disease activity and were not affected by immunosuppressive treatment. We also document, for the first time, that, in AILD, bona\u2010fide Tregs produce less interleukin (IL)\u221210 and are impaired in their ability to suppress CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup> target cell proliferation, a feature that in HSs, but not in AILDs, is dependent, at least in part, on IL\u201010 secretion. Decreased IL\u201010 production by Tregs in AILD is linked to poor responsiveness to IL\u20102 and phospho signal transducer and activator of transcription 5 up\u2010regulation. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Tregs are numerically impaired in AILD, this impairment being more prominent during active disease. Notably, defective IL\u201010 production, resulting from low Treg responsiveness to IL\u20102, contributes to Treg functional impairment. (H<jats:sc>epatology<\/jats:sc> 2015;62:863\u2013875)<\/jats:p>","DOI":"10.1002\/hep.27884","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T08:02:49Z","timestamp":1431072169000},"page":"863-875","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":99,"title":["In autoimmune hepatitis type 1 or the autoimmune hepatitis\u2013sclerosing cholangitis variant defective regulatory T\u2010cell responsiveness to IL\u20102 results in low IL\u201010 production and impaired suppression"],"prefix":"10.1097","volume":"62","author":[{"given":"Rodrigo","family":"Liberal","sequence":"first","affiliation":[{"name":"Department of Liver Studies,Division of Transplantation Immunology & Mucosal Biology, MRC Center for Transplantation, King's College London, Faculty of Life Sciences & Medicine,London,United Kingdom"},{"name":"Faculty of Medicine,University of Porto,Porto,Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte R.","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Liver Studies,Division of Transplantation Immunology & Mucosal Biology, MRC Center for Transplantation, King's College London, Faculty of Life Sciences & Medicine,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth S.","family":"Holder","sequence":"additional","affiliation":[{"name":"Department of Liver Studies,Division of Transplantation Immunology & Mucosal Biology, MRC Center for Transplantation, King's College London, Faculty of Life Sciences & Medicine,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Cardone","sequence":"additional","affiliation":[{"name":"Department of Liver Studies,Division of Transplantation Immunology & Mucosal Biology, MRC Center for Transplantation, King's College London, Faculty of Life 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