Models to explore the molecular function and regulation of AIRE

Mutations in the Autoimmune Regulator (AIRE) gene are responsible for Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED). Within the thymic medulla, AIRE regulates the expression of a large number of tissue-specific self-antigens (TSAs) and the recognisation of these TSAs by auto-reactive T-cells is a prerequisite step for thymic negative selection. APECED patients will therefore develop multi-organ autoimmune disease because of the defective role of AIRE in thymic negative selection. Aire-deficient mice also develop multi-organ autoimmune disease and in this review we will focus on how both animal and cellular models have been used to dissect biochemical function of AIRE/Aire which is an essential step toward the understanding disease pathogenesis.