ArticleHepatology (Baltimore, Md.)2016
Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 115 citations in OpenAlex.
- Liver Fibrosis and Purinergic Signaling: Autocrine-Paracrine Role of ATP in Liver Damage.International journal of molecular sciences · 2026Review
- JAK/STAT signaling in liver disease: a therapeutic target or a context-dependent double-edged sword?Journal of translational medicine · 2026Review
- Tissue-resident macrophage survival depends on mitochondrial function regulated by SerpinB2 in chronic inflammation.Nature communications · 2026Article
- Immune cell remodelling and the peribiliary immune niche in primary biliary cholangitis: from initiation to chronicity.eGastroenterology · 2026Review
- Cell-specific epigenome-wide DNA methylation in peripheral CD4(+) lymphocytes from patients with primary biliary cholangitis.Journal of translational autoimmunity · 2025Article
- Effect of rapamycin nanoparticles in an animal model of primary biliary cholangitis.World journal of hepatology · 2025Article
- Double-negative T cells in combination with ursodeoxycholic acid ameliorates immune-mediated cholangitis in mice.BMC medicine · 2025Article
- Common pathological mechanisms and therapeutic strategies in primary Sjogren's syndrome and primary biliary cholangitis: from tissue immune microenvironment to targeted therapy.Frontiers in immunology · 2025Review
- Chronic Low-Level IFN-γ Expression Disrupts Mitochondrial Complex I Activity in Renal Macrophages: An Early Mechanistic Driver of Lupus Nephritis Pathogenesis.International journal of molecular sciences · 2024Article
- Single-cell RNA sequencing reveals the pro-inflammatory roles of liver-resident Th1-like cells in primary biliary cholangitis.Nature communications · 2024Article
- Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females.Cell metabolism · 2024Article
- Dietary therapy of murine primary biliary cholangitis induces hepatocellular steatosis: A cautionary tale.Liver international : official journal of the International Association for the Study of the Liver · 2024Article
- Cross-Species Studies Reveal That Dysregulated Mitochondrial Gene Expression and Electron Transport Complex I Activity Are Crucial for Sarcopenia.International journal of molecular sciences · 2024Article
- Epigenetic disease markers in primary sclerosing cholangitis and primary biliary cholangitis-methylomics of cholestatic liver disease.Hepatology communications · 2024Article
- Are Gender Differences Important for Autoimmune Liver Diseases?Life (Basel, Switzerland) · 2024Review
- Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis.Hepatology communications · 2024Article
- Review
- Animal models of primary biliary cholangitis: status and challenges.Cell & bioscience · 2023Review
- Sex differences in chronic liver disease and benign liver lesions.JHEP reports : innovation in hepatology · 2023Review
- IFN-γ and androgens disrupt mitochondrial function in murine myocytes.The Journal of pathology · 2023Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
Abstract
unlabelledIn 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.
conclusionChanges in IFNγ expression are critical for the pathogenesis of PBC. (Hepatology 2016;64:1189-1201).
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