The autoimmune regulator gene, which is defective in the hereditary auto-immune disease APECED, encodes the transcriptional activator AIRE. AIRE is expressed in the medullary epithelial cells and monocyte-dendritic cells of the thymus, with lower expression in the spleen, fetal liver and lymph nodes. In adult tissue, AIRE expression in the thymus is confined to the medulla and the cortico-medullary junction, where it is modulated by thymocytes undergoing negative selection. At the cellular level, AIRE is located in microtubular structures of the cyto-skeleton and in discrete nuclear dots resembling ND10 nuclear bodies. AIRE is induced by developing early thymocytes and is associated with the correct establishment of a regular thymic environment. AIRE regulates thymic architecture via transcriptional control of downstream target genes. AIRE mutations in APECED patients may affect thymic T cell selection and the formation of self-tolerance.