The autoimmune regulator gene (AIRE) is a transcription factor expressed both in 
the thymus, by medullary thymic epithelial cells, and in secondary lymphoid 
organs. AIRE controls the local transcription of organ- specific proteins 
typically expressed in peripheral tissues, thus allowing the negative selection 
of self- reactive T cells. The crucial role played by AIRE in central immune 
tolerance emerged in the studies on the pathogenesis of Autoimmune 
Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy, a rare inherited 
polyendocrine/autoimmune disease. Thereafter, several studies found evidences 
indicating that AIRE impairment might be pathogenically involved in several 
autoimmune diseases and in tumorigenesis. In this review, we focus on recent 
advances relative to AIRE's effect on T cell development in physiology and 
disease. In particular, we address the following issues: 1) AIRE function and 
mTECs biology, 2) the impact of AIRE gene mutations in autoimmune diseases, and 
3) the role of AIRE gene in anti-tumor immune response.