The role of androgens in autoimmune liver diseases
Women are more prone to develop the autoimmune liver diseases autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Affected men, on the other hand, show a more severe course of disease. Indeed, sex differences in autoimmune liver diseases are among the strongest of all autoimmune diseases. Autoimmune liver diseases are rare diseases which are difficult to treat and thus often lead to liver cirrhosis and death. Due to the lack of understanding disease pathogenesis causal treatment is not available. Understanding mechanisms leading to autoimmunity in the liver is crucial in order to develop targeted treatment strategies. Suitable animal models to study sex differences in AIH or PBC had been lacking. We have developed an inducible mouse model of autoimmune cholangitis, which shows female predominance similar to PBC and with male resistance to liver inflammation attributed to the protective effects of testosterone. Based on our previous and preliminary data from mouse models and human studies we here hypothesize that androgens play a critical role in the development and progression of autoimmune liver diseases by modulating T cells directly or indirectly via antigen presenting cells.
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* equally contributing authors
