{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:16:00Z","timestamp":1792451760137,"version":"4.5.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A subset of human regulatory T cells (Tregs) can secrete IFN-\u03b3 or IL-17, and thus share features of TH1 or TH17 effector cells and lose suppressive function. The main factors driving this differentiation of Tregs toward a proinflammatory phenotype include IL-12 for TH1-like and IL-6 for TH17-type Tregs. In this study we show that Tregs of patients with de novo autoimmune hepatitis (dAIH) display increased frequencies of proinflammatory IFN-\u03b3 and IL-17 cytokines. Irrespective of a fully demethylated FOXP3 locus, Tregs of subjects with dAIH are functionally impaired. In line with the observed Treg phenotype, we detected the presence of two dominant cytokines (IL-12 and IL-6) clustering with CD68+ monocyte\/macrophage cells in livers of subjects with dAIH, and isolated monocytes of subjects with dAIH secrete high levels of proinflammatory IL-12 and IL-6, suggesting that this inflammatory milieu is key for functional impairment of Tregs. Importantly, the blockade of IFN-\u03b3 partially restores suppressive function of Tregs of subjects with dAIH, indicating that monocyte\/macrophage-derived triggers might play a central role in Treg dysfunction and pathogenesis of dAIH.<\/jats:p>","DOI":"10.4049\/jimmunol.1502276","type":"journal-article","created":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T22:49:45Z","timestamp":1461019785000},"page":"4040-4051","source":"Crossref","is-referenced-by-count":68,"title":["Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells"],"prefix":"10.1093","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3817-890X","authenticated-orcid":false,"given":"Adam S","family":"Arterbery","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awo","family":"Osafo-Addo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron","family":"Avitzur","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Toronto , Toronto, Ontario MSG 1X8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ciarleglio","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale School of Public Health , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Deng","sequence":"additional","affiliation":[{"name":"Yale Center for Analytic Sciences, Yale School of Public Health , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J","family":"Lobritto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Columbia University , New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Columbia University , New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Hafler","sequence":"additional","affiliation":[{"name":"Department of Neurology and Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Kleinewietfeld","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathobiochemistry, Medical Faculty Carl Gustav Carus, Dresden University of Technology , 01307 Dresden ,","place":["Germany"]},{"name":"VIB Laboratory of Translational Immunomodulation, Biomedical Research Institute, Hasselt University , BE3590 Diepenbeek ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-112X","authenticated-orcid":false,"given":"Udeme D","family":"Ekong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,5,15]]},"reference":[{"key":"2025030702164351100_r1","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1111\/j.1600-6143.2006.01717.x","article-title":"Rejection and steroid dependence: unique risk factors in the development of pediatric posttransplant de novo autoimmune hepatitis","volume":"7","author":"Venick","year":"2007","journal-title":"Am. 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