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http://purl.uniprot.org/citations/27178326http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27178326http://www.w3.org/2000/01/rdf-schema#comment"

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In most autoimmune diseases the serologic hallmarks of disease precede clinical pathology by years. Therefore, the use of animal models in defining early disease events becomes critical. We took advantage of a "designer" mouse with dysregulation of interferon gamma (IFNγ) characterized by prolonged and chronic expression of IFNγ through deletion of the IFNγ 3'-untranslated region adenylate uridylate-rich element (ARE). The ARE-Del(-/-) mice develop primary biliary cholangitis (PBC) with a female predominance that mimics human PBC that is characterized by up-regulation of total bile acids, spontaneous production of anti-mitochondrial antibodies, and portal duct inflammation. Transfer of CD4 T cells from ARE-Del(-/-) to B6/Rag1(-/-) mice induced moderate portal inflammation and parenchymal inflammation, and RNA sequencing of liver gene expression revealed that up-regulated genes potentially define early stages of cholangitis. Interestingly, up-regulated genes specifically overlap with the gene expression signature of biliary epithelial cells in PBC, implying that IFNγ may play a pathogenic role in biliary epithelial cells in the initiation stage of PBC. Moreover, differentially expressed genes in female mice have stronger type 1 and type 2 IFN signaling and lymphocyte-mediated immune responses and thus may drive the female bias of the disease.

Conclusion

Changes in IFNγ expression are critical for the pathogenesis of PBC. (Hepatology 2016;64:1189-1201)."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.org/dc/terms/identifier"doi:10.1002/hep.28641"xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Feng D."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Gao B."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Kim S."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Valencia J.C."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Park O."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Yang G.X."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Tsuneyama K."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Baba N."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Young H.A."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Gershwin M.E."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Leung P.S."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Hodge D.L."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Bae H.R."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Back T."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Karwan M."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/author"Merchant A.S."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/name"Hepatology"xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/pages"1189-1201"xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/title"Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance."xsd:string
http://purl.uniprot.org/citations/27178326http://purl.uniprot.org/core/volume"64"xsd:string
http://purl.uniprot.org/citations/27178326http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27178326