Both female mice and female humans have a well-known predisposition to autoimmune disease. In the Journal of Clinical Investigation, Berrih-Aknin and colleagues demonstrate that sex hormones have an important influence on thymic central tolerance. Medullary thymic epithelial cells from female humans or from female mice have lower expression of AIRE, a transcription factor involved in imposing central tolerance, than those of their male counterparts. The expression of tissue-restricted antigens controlled by AIRE is similarly lower in females. Estrogen negatively regulates AIRE expression, and the effects of this female sex hormone are in turn antagonized by testosterone. Loss of the main estrogen receptor in medullary thymic epithelial cells from female mice restores the expression of AIRE and tissue-restricted antigens. Conversely, castration of male mice diminishes AIRE expression, and knockdown of AIRE enhances susceptibility to autoimmune thyroiditis. Sex hormones therefore serve an important role in shaping self-tolerance in the thymus and influence predisposition to autoimmunity.
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Fehervari, Z. Gender imbalance. Nat Immunol 17, 480 (2016). https://doi.org/10.1038/ni.3452
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DOI: https://doi.org/10.1038/ni.3452
