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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: UNLABELLED. Meshes: Animals, Autoimmune Diseases, Cholangitis, Crosses, Genetic, Cytokines, Enzyme-Linked Immunosorbent Assay, Female, Liver Cirrhosis, Biliary, Lymphocyte Count, Male, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mitochondria, Polymerase Chain Reaction, T-Lymphocytes, Regulatory.
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Does deficiency in regulatory T cells result in development of antimitochondrial antibodies and autoimmune cholangitis? Context: There 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.
assistant
The 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. Final Decision: yes