ArticleHepatology (Baltimore, Md.)2011
Innate immunity and primary biliary cirrhosis: activated invariant natural killer T cells exacerbate murine autoimmune cholangitis and fibrosis.
Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 96 citations in OpenAlex.
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- Natural Killer T cells promote cholestatic liver disease independent of antigen presentation by cholangiocytes.Hepatology communications · 2026Article
- Modulation of Inflammation-Driven Hepatocarcinogenesis: The Hepatic Immune Microenvironment, Gut-Liver Axis, and Neuroregulation.Journal of hepatocellular carcinoma · 2026Review
- The Treatment of Primary Biliary Cholangitis: Time for Personalized Medicine.Clinical reviews in allergy & immunology · 2025Review
- The impact of T cells on immune-related liver diseases: an overview.Inflammation and regeneration · 2025Review
- Single-cell RNA sequencing reveals the pro-inflammatory roles of liver-resident Th1-like cells in primary biliary cholangitis.Nature communications · 2024Article
- Regulatory T cells in inflamed liver are dysfunctional in murine primary biliary cholangitis.Clinical and experimental immunology · 2024Article
- IL-21, not IL-17A, exacerbates murine primary biliary cholangitis.Clinical and experimental immunology · 2024Article
- Single-cell RNA sequencing reveals a peripheral landscape of immune cells in Schistosomiasis japonica.Parasites & vectors · 2023Article
- Apoptotic biliary epithelial cells and gut dysbiosis in the induction of murine primary biliary cholangitis.Journal of translational autoimmunity · 2023Article
- Regulatory mechanism of HIF-1α and its role in liver diseases: a narrative review.Annals of translational medicine · 2022Review
- Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis.Frontiers in immunology · 2022Review
- Interleukin-30 Suppresses Not Only CD4Biomedicines · 2021Article
- Rodent models of cholestatic liver disease: A practical guide for translational research.Liver international : official journal of the International Association for the Study of the Liver · 2021Review
- Animal Models of Autoimmune Liver Diseases: a Comprehensive Review.Clinical reviews in allergy & immunology · 2020Review
- T Cells in Fibrosis and Fibrotic Diseases.Frontiers in immunology · 2020Review
- Preclinical insights into cholangiopathies: disease modeling and emerging therapeutic targets.Expert opinion on therapeutic targets · 2019Review
- Deviations in Peripheral Blood Cell Populations are Associated with the Stage of Primary Biliary Cholangitis and Presence of Itching.Archivum immunologiae et therapiae experimentalis · 2018Article
- Endogenous IL-10 maintains immune tolerance but IL-10 gene transfer exacerbates autoimmune cholangitis.Journal of autoimmunity · 2018Article
- Mesenchymal stem cells alleviate experimental autoimmune cholangitis through immunosuppression and cytoprotective function mediated by galectin-9.Stem cell research & therapy · 2018Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
Abstract
unlabelledMurine 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 α-galactosylceramide (α-GalCer), an invariant natural killer T cell activator. Importantly, we report herein that 2-OA-BSA-immunized mice exposed to α-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.
conclusionOur 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.