ArticleClinical and experimental immunology2011
The multi-hit hypothesis of primary biliary cirrhosis: polyinosinic-polycytidylic acid (poly I:C) and murine autoimmune cholangitis.
Article in Clinical and experimental immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- [Exploring the research on the molecular mechanisms of autoimmune liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models.BMC gastroenterology · 2024Article
- Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Mouse Model of IL-17-Dominant Rhinitis Using Polyinosinic-Polycytidylic Acid.Allergy, asthma & immunology research · 2017Article
- Serum Metabolomics Analysis Reveals a Distinct Metabolic Profile of Patients with Primary Biliary Cholangitis.Scientific reports · 2017Article
- Review on Toll-Like Receptor Activation in Myasthenia Gravis: Application to the Development of New Experimental Models.Clinical reviews in allergy & immunology · 2017Review
- Eosinophils in Autoimmune Diseases.Frontiers in immunology · 2017Review
- Adaptive immunity in the liver.Cellular & molecular immunology · 2016Review
- Primary biliary cirrhosis: From bench to bedside.World journal of gastrointestinal pharmacology and therapeutics · 2015Review
- Animal models in primary biliary cirrhosis and primary sclerosing cholangitis.Clinical reviews in allergy & immunology · 2015Review
- Innate immunity drives the initiation of a murine model of primary biliary cirrhosis.PloS one · 2015Article
- Murine autoimmune cholangitis requires two hits: cytotoxic KLRG1(+) CD8 effector cells and defective T regulatory cells.Journal of autoimmunity · 2014Article
- Aberrant TGF-β1 signaling contributes to the development of primary biliary cirrhosis in murine model.World journal of gastroenterology · 2013Article
- Etiopathogenesis of primary biliary cirrhosis: an overview of recent developments.Hepatology international · 2013Article
- Therapeutic effect of cytotoxic T lymphocyte antigen 4/immunoglobulin on a murine model of primary biliary cirrhosis.Hepatology (Baltimore, Md.) · 2013Article
- Identification of potential cytokine pathways for therapeutic intervention in murine primary biliary cirrhosis.PloS one · 2013Article
- Role of autoimmunity in primary biliary cirrhosis.World journal of gastroenterology · 2012Review
- Immunological orchestration of liver fibrosis.Clinical reviews in allergy & immunology · 2012Review
- The role of natural killer (NK) and NK T cells in the loss of tolerance in murine primary biliary cirrhosis.Clinical and experimental immunology · 2012Article
- Toll-like receptors in liver fibrosis: cellular crosstalk and mechanisms.Frontiers in physiology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
A void in understanding primary biliary cirrhosis (PBC) is the absence of appropriate animal models. Our laboratory has studied a murine model of autoimmune cholangitis induced following immunization with 2-octynoic acid (2OA), an antigen identified following extensive quantitative structural activity relationship (QSAR) analysis, using human autoantibodies and three-dimensional analysis of the mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). Mice immunized with 2OA coupled to bovine serum albumin (BSA) develop anti-mitochondrial antibodies (AMAs) of the identical specificity as humans with PBC, and in addition develop inflammatory portal cell infiltrates in liver. However, the natural history of disease is less severe than in humans and does not include fibrosis. Data from human and autoimmune murine models suggest that environmental and/or infectious agents can exacerbate autoimmune reactions, and a model of PBC has been described in which polyinosinic-polycytidylic acid (poly I:C), a viral RNA mimetic and Toll-like receptor 3 (TLR-3) agonist induces low-titre AMAs and in mild portal infiltrates. We took advantage of our established model to determine whether immunization with 2OA-BSA coupled with poly I:C alters the disease process. Indeed, the addition of poly I:C produces a profound exacerbation of autoimmune cholangitis, including a significant increase in CD8(+) infiltrating T cells, as well as a marked increase of proinflammatory cytokines. In addition, mice have evidence of fibrosis. These findings lend support to the concept that besides breakdown of self-tolerance, there is a requirement of a second 'hit' during the breakdown process that leads to disease which more faithfully mimics human PBC.
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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.