{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:40:15Z","timestamp":1790005215069,"version":"4.0.1"},"reference-count":45,"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":1645,"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":[[2011,3]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>\n                                 <jats:bold>Murine models of autoimmunity allow the study of the earliest events in disease pathogenesis. Our laboratory has developed a xenobiotic induced model of primary biliary cirrhosis (PBC) following immunization of mice with 2-octynoic acid coupled to bovine serum albumin (2-OA-BSA), an antigen selected following quantitative structure-activity relationship analysis of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the immunodominant autoantigen of PBC. Recent data in humans with PBC has suggested that a major component of liver pathology is due to activation of innate immunity. We took advantage of our 2-OA-BSA model and immunized mice with and without the addition of \u03b1-galactosylceramide (\u03b1-GalCer), an invariant natural killer T cell activator. Importantly, we report herein that 2-OA-BSA-immunized mice exposed to \u03b1-GalCer develop a profound exacerbation of their autoimmune cholangitis, including significant increases in CD8+ T-cell infiltrates, portal inflammation, granuloma formation, and bile duct damage. Furthermore, such mice produce increased levels of antimitochondrial antibodies and have evidence of fibrosis, a feature not previously reported in the murine models of PBC.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Our data suggests a primary role of innate immunity in the exacerbation of autoimmune cholangitis and also become a logical explanation for the recurrence of PBC following liver transplantation in the absence of major histocompatability complex compatibility. We submit that PBC begins with loss of tolerance to PDC-E2 and a multilineage antimitochondrial response in which autoreactive CD8+ T cells are critical. However, the perpetuation of disease and its exacerbation will also be modulated by innate immune mechanisms. (Hepatology 2011;)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.24113","type":"journal-article","created":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T20:59:49Z","timestamp":1292360389000},"page":"915-925","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":87,"title":["Innate Immunity and Primary Biliary Cirrhosis: Activated Invariant Natural Killer T Cells Exacerbate Murine Autoimmune Cholangitis and Fibrosis \u00a7\u0394"],"prefix":"10.1097","volume":"53","author":[{"given":"Si-Jie","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Hsu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tsuneyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick 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