{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:36:09Z","timestamp":1790922969164,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Regulatory CD4<jats:sup>+<\/jats:sup> T cells (Tregs) are pivotal for inhibition of autoimmunity. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology where contribution of Tregs is still unclear. Activation of the JAK\u2010STAT pathway critically modifies functions of Tregs. In PSC, we studied activation of STAT proteins and Treg functions in response to cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 51 patients with PSC, 10 disease controls (chronic replicative hepatitis C), and 36 healthy controls we analyzed frequencies of Foxp3<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>CD127<jats:sup>low<\/jats:sup>CD4<jats:sup>+<\/jats:sup> Tregs, their expression of ectonucleotidase CD39, and cytokine\u2010induced phosphorylation of STAT1, 3, 5, and 6 using phospho\u2010flow cytometry. In parallel, we measured cytokines IFN\u2010gamma, interleukin (IL)\u20106, IL\u20102, and IL\u20104 in serum via bead\u2010based immunoassays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In patients with PSC, <jats:italic>ex vivo<\/jats:italic> frequencies of peripheral Tregs and their expression of CD39 were significantly reduced (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05 each). Furthermore, serum levels of IFN\u2010gamma, IL\u20106, IL\u20102, and IL\u20104 were markedly higher in PSC (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05 each). Unlike activation of STAT1, STAT5, and STAT6, IL\u20106 induced increased phosphorylation of STAT3 in Tregs of PSC\u2010patients (<jats:italic>p<\/jats:italic>\u2009=\u2009.0434). Finally, STAT3 activation in Tregs correlated with leukocyte counts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In PSC, we observed enhanced STAT3 responsiveness of CD4<jats:sup>+<\/jats:sup> Tregs together with reduced CD39 expression probably reflecting inflammatory activity of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.1248","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T13:30:14Z","timestamp":1712928614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["STAT activation in regulatory CD4<sup>+<\/sup> T cells of patients with primary sclerosing cholangitis"],"prefix":"10.1002","volume":"12","author":[{"given":"Leona","family":"Dold","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn Bonn Germany"},{"name":"German Center for Infection Research (DZIF) Partner Site 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