Dataset Information


Sex Bias in CNS Autoimmune Disease Mediated by Androgen Control of Autoimmune Regulator

ABSTRACT: Male gender is protective against multiple sclerosis and other T cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well-understood. Autoimmune Regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here, we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared to females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. Overall design: RNA-seq comparison of male vs. female expression in mTEC cells. Pools of 10 mice each were used for each replicate (two for male and two for female)

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

ORGANISM(S): Mus musculus  

SUBMITTER: Joshua Starmer 




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