| Description: |
AIRE (AutoImmune REgulator) is a transcription factor that plays an essential role to promote self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the periphery, called tissue restricted antigens (TRA) [, ]. Mutations cause a rare autosomal recessively inherited disease termed APECED. APECED, also called Autoimmune Polyglandular Syndrome type I (APS 1), is the only described autoimmune disease with established monogenic background, being localised outside the major histocompatibility complex region. It is characterised by the presence of two of the three major clinical entities, chronic mucocutaneus candidiasis, hypoparathyroidism and Addison's disease. Other immunologically mediated phenotypes, including insulin-dependent diabetes mellitus (IDDM), gonadal failure, chronic gastritis, vitiligo, autoimmune thyroid disease, enamel hypoplasia, and alopecia may also be present. Immunologically, APECED patients have deficient T cell responses towards Candida antigens, and clinical symptoms both within and outside the endocrine system, mainly as a result of autoimmunity against organ-specific autoantigens [, ].AIRE has a HSR/CARD domain involved in promoting AIRE to multimerise to itself, a SAND domain that appears to be involved in promoting a protein-protein interaction with a transcriptional repressive complex and two zinc fingers of the plant homodomain (PHD) type PHD1 and PHD2, of which PHD1 functions as a histone code reader [, , , ].AIRE has a dual subcellular location. It is not only expressed in multiple immunologically relevant tissues, such as the thymus, spleen, lymph nodes and bone marrow, but it has also been detected in various other tissues, such as kidney, testis, adrenal glands, liver and ovary, suggesting that APECED proteins might also have a function outside the immune system. However, AIRE is not expressed in the target organs of autoimmune destruction. At the subcellular level, AIRE can be found in the cell nucleus in a speckled pattern in domains resembling promyeolocytic leukaemia nuclear bodies, also known as ND10, nuclear dots or potential oncogenic domains associated with the AIRE homologous nuclear proteins Sp100, Sp140, and Lysp100. |
