{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:49Z","timestamp":1791312709598,"version":"4.3.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2018,2,18]],"date-time":"2018-02-18T00:00:00Z","timestamp":1518912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,2,18]],"date-time":"2018-02-18T00:00:00Z","timestamp":1518912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>\n                    We have reported on a murine model of autoimmune cholangitis, generated by altering the AU\u2010rich element (ARE) by deletion of the interferon gamma (IFN\u2010\u03b3) 3' untranslated region (coined ARE\u2010Del\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ), that has striking similarities to human primary biliary cholangitis (PBC) with female predominance. Previously, we suggested that the sex bias of autoimmune cholangitis was secondary to intense and sustained type I and II IFN signaling. Based on this thesis, and to define the mechanisms that lead to portal inflammation, we specifically addressed the hypothesis that type I IFNs are the driver of this disease. To accomplish these goals, we crossed ARE\u2010Del\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice with IFN type I receptor alpha chain (Ifnar1) knockout mice. We report herein that loss of type I IFN receptor signaling in the double construct of ARE\u2010Del\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    Ifnar1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice dramatically reduces liver pathology and abrogated sex bias. More importantly, female ARE\u2010Del\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice have an increased number of germinal center (GC) B cells as well as abnormal follicular formation, sites which have been implicated in loss of tolerance. Deletion of type I IFN signaling in ARE\u2010Del\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    Ifnar1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice corrects these GC abnormalities, including abnormal follicular structure.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Our data implicate type I IFN signaling as a necessary component of the sex bias of this murine model of autoimmune cholangitis. Importantly these data suggest that drugs that target the type I IFN signaling pathway would have potential benefit in the earlier stages of PBC. 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