Autoimmune regulator functions in autoimmunity control

Abstract

Mutation of the autoimmune regulator (AIRE) gene is responsible for the development of autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), an organ-specific autoimmune disease with monogenic autosomal recessive inheritance. AIRE is strongly expressed in thymic epithelial cells (TECs), and its structural features suggest that it probably acts as a transcriptional regulator. The role of Aire in the elimination of autoreactive T cells (i.e., negative selection) has been well demonstrated with the use of transgenic mouse models, although how Aire regulates this process in TECs has yet to be determined. Aire also regulates other features of autoimmunity, such as target-organ specificity of autoimmune destruction, suggesting that an understanding of the relationship between AIRE gene malfunction and the breakdown of self-tolerance promises to help unravel the pathogenesis of not only APECED but also other types of autoimmune diseases. Owing to this unique tolerogenic function of Aire, the cellular origin and developmental process of Aire-expressing TECs is now becoming an interesting field for intense research.