ArticleHepatology (Baltimore, Md.)2009
Deficiency in regulatory T cells results in development of antimitochondrial antibodies and autoimmune cholangitis.
Article in Hepatology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 98 citations in OpenAlex.
- Interleukin-1 receptor antagonist autoantibodies in Still's disease: Mechanistic insights and laboratory testing.World journal of methodology · 2026Review
- Latent Tubulointerstitial Nephritis with IgM-positive Plasma Cells Uncovered in a Case of IgA Nephropathy and Primary Biliary Cholangitis: Clinical and Histological Insights.Internal medicine (Tokyo, Japan) · 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
- ProbioticNutrients · 2024Article
- Animal models of primary biliary cholangitis: status and challenges.Cell & bioscience · 2023Review
- Regulatory T-cell deficiency leads to features of autoimmune liver disease overlap syndrome in scurfy mice.Frontiers in immunology · 2023Article
- Linking Human Betaretrovirus with Autoimmunity and Liver Disease in Patients with Primary Biliary Cholangitis.Viruses · 2022Review
- Interplay between Mast Cells and Regulatory T Cells in Immune-Mediated Cholangiopathies.International journal of molecular sciences · 2022Review
- X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.Gastroenterology · 2021Article
- Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis.Pathologica · 2021Review
- Deletion of Mcpip1 in Mcpip1Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Regulatory T cells in autoimmune hepatitis: an updated overview.Journal of autoimmunity · 2021Review
- 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
- Cholangiopathies - Towards a molecular understanding.EBioMedicine · 2018Review
- Regulatory T-cell conditioning endows activated effector T cells with suppressor function in autoimmune hepatitis/autoimmune sclerosing cholangitis.Hepatology (Baltimore, Md.) · 2017Article
- DNA-binding properties of FOXP3 transcription factor.Acta biochimica et biophysica Sinica · 2017Article
- Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis.Frontiers in immunology · 2017Review
- Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance.Hepatology (Baltimore, Md.) · 2016Article
- Single-gene association between GATA-2 and autoimmune hepatitis: A novel genetic insight highlighting immunologic pathways to disease.Journal of hepatology · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
unlabelledThere have been several descriptions of mouse models that manifest select immunological and clinical features of autoimmune cholangitis with similarities to primary biliary cirrhosis in humans. Some of these models require immunization with complete Freund's adjuvant, whereas others suggest that a decreased frequency of T regulatory cells (Tregs) facilitates spontaneous disease. We hypothesized that antimitochondrial antibodies (AMAs) and development of autoimmune cholangitis would be found in mice genetically deficient in components essential for the development and homeostasis of forkhead box 3 (Foxp3)(+) Tregs. Therefore, we examined Scurfy (Sf) mice, animals that have a mutation in the gene encoding the Foxp3 transcription factor that results in a complete abolition of Foxp3(+) Tregs. At 3 to 4 weeks of age, 100% of animals exhibit high-titer serum AMA of all isotypes. Furthermore, mice have moderate to severe lymphocytic infiltrates surrounding portal areas with evidence of biliary duct damage, and dramatic elevation of cytokines in serum and messenger RNAs encoding cytokines in liver tissue, including tumor necrosis factor alpha, interferon-gamma, interleukin (IL)-6, IL-12, and IL-23.
conclusionThe lack of functional Foxp3 is a major predisposing feature for loss of tolerance that leads to autoimmune cholangitis. These findings reflect on the importance of regulatory T cells in other murine models as well as in patients with primary biliary cirrhosis.
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