{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:15:21Z","timestamp":1785795321018,"version":"3.56.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2253,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>Interface hepatitis, the histological lesion typical of autoimmune hepatitis (AIH), is composed of CD4 and CD8 T lymphocytes and of innate immunity cells, particularly monocytes. Studies in AIH have focused on autoreactive CD4 and CD8 T cells and impairment of CD4+CD25+ regulatory T cells (T-regs), whereas little is known about the role of monocytes and their relationship with T-regs. We have investigated 51 patients with autoimmune liver disease (AILD) and 27 healthy subjects, finding that monocytes were higher in number (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.044), had a more vigorous spontaneous migration (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0005 in patients with inactive disease [ID], and <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001 in those with active disease [AD]), displayed a higher tumor necrosis factor alpha (TNF-\u03b1) over interleukin (IL)-10 production (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.07 in ID and <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.0005 in AD), and expressed higher levels of Toll-like receptor (TLR) 4 (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.048 in ID and <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.03 in AD). Addition of conventional T-regs (cT-regs) in AILD enhanced monocyte migration (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.05 in ID and <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.08 in AD), magnified TNF-\u03b1 over IL-10 production (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.0005 in ID and <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.006 in AD), and markedly increased TLR4 expression levels (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.01 in ID and <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.004 in AD), whereas in normal subjects it either restrained or left unchanged monocyte function. Because a CD127-negative subpopulation within CD4+CD25+ T cells exerts the strongest regulatory activity, we performed additional experiments using purified CD4+CD25+CD127\u2212 T cells (true T-regs [tT-regs]). Addition of tT-regs to monocytes decreased monocyte migration (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.03) and promoted IL-10 production (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.009), leaving unchanged TLR4 expression in healthy subjects, whereas in patients with AILD it induced only a marginal increase in IL-10 production (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.045 in ID and <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.13 in AD). <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Monocyte overactivation and inability of cT-regs and tT-regs to restrain it may contribute to the loss of immune tolerance and perpetuation of the autoimmune attack in AILD. (Hepatology 2009.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.22914","type":"journal-article","created":{"date-parts":[[2009,2,18]],"date-time":"2009-02-18T21:22:24Z","timestamp":1234992144000},"page":"130-142","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":74,"title":["Vigorous activation of monocytes in juvenile autoimmune liver disease escapes the control of regulatory T-cells #"],"prefix":"10.1097","volume":"50","author":[{"given":"Maria Serena","family":"Longhi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragai 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