Human Autoimmune Regulator (AIRE) Protein

Background

The Autoimmune Regulator (AIRE) is a protein encoded by the AIRE gene, and it plays a critical role in immune tolerance and the prevention of autoimmune diseases. AIRE is primarily expressed in a specialized type of cell called medullary thymic epithelial cells (mTECs) found in the thymus gland. AIRE functions as a transcriptional regulator, controlling the expression of a wide range of tissue-specific antigens (TSAs) within mTECs. These TSAs represent proteins that are normally expressed in various tissues. By inducing the expression of TSAs in the thymus, AIRE ensures that developing T cells encounter a diverse array of self-antigens during their maturation process.The exposure of developing T cells to self-antigens in the thymus is crucial for their selection and education. T cells that recognize self-antigens too strongly or too weakly are eliminated or rendered tolerant, respectively, through a process known as central tolerance. AIRE-mediated expression of TSAs in mTECs is a key mechanism by which central tolerance is maintained, helping to prevent the development of autoimmune responses against self-tissues. Mutations in the AIRE gene lead to a rare autoimmune disorder known as autoimmune polyendocrine syndrome type 1 (APS-1), also called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). APS-1 is characterized by the development of multiple autoimmune diseases affecting various endocrine organs, such as the adrenal glands, parathyroid glands, and pancreas, as well as other tissues. These autoimmune manifestations result from defects in central tolerance due to impaired AIRE function, leading to the escape of autoreactive T cells from thymic deletion.