Autoimmune regulator

The autoimmune regulator (AIRE) is a is_associated_with::protein that in humans is encoded by the AIRE is_associated_with::gene. AIRE is a is_associated_with::transcription factor expressed in the medulla of the is_associated_with::thymus and controls the mechanism that prevents the immune system from attacking the body itself.

Each is_associated_with::T cell attacks a foreign substance presented within a MHC molecule which it identifies with its receptor. T cells have receptors which are generated by randomly shuffling gene segments. Each T cell attacks a different substance. T cells that attack the body's own proteins are eliminated in the thymus. Medullary thymic epithelial cells (mTECs) express major proteins from elsewhere in the body (so called "tissue-specific self-antigens" - TSAs), and T cells that respond to those proteins are eliminated through cell death(is_associated_with::apoptosis), thus it is thought that AIRE therefore drives negative selection.

The AIRE controls the expression of those thymic epithelial cells in the medulla (inner part) of the thymus. When AIRE is defective, T cells can attack the body, resulting in is_associated_with::autoimmune disease.

Function
In the thymus, the autoimmune regulator causes transcription of a wide selection of organ-specific genes that create is_associated_with::proteins that are usually only expressed in peripheral tissues, creating an "immunological self-shadow" in the thymus. It is important that self-reactive is_associated_with::T cells that bind strongly to self-is_associated_with::antigen are eliminated in the thymus (via the process of negative selection), otherwise they can later bind to their corresponding self-proteins and create an autoimmune reaction. So the expression of non-local proteins by AIRE reduces the threat of the occurrence of is_associated_with::autoimmunity later on by allowing for the elimination of auto-reactive is_associated_with::T cells that bind antigens not traditionally found in the thymus. Furthermore, it has been found that AIRE is expressed in a population of stromal cells located in secondary lymphoid tissues, however these cells appear to express a distinct set of TSAs compared to mTECs

Research in knockout mice has demonstrated that Aire functions through initiating the transcription of a diverse set of self-antigens, such as is_associated_with::insulin, in the is_associated_with::thymus. This expression then allows maturing is_associated_with::thymocytes to become tolerant towards peripheral organs, thereby suppressing autoimmune disease.

The AIRE gene is expressed in many other tissues as well. AIRE gene is also expressed in the 33D1+ subset of dendritic cells in mouse and in human dendritic cells.

Pathology
The autoimmune regulator is mutated in the rare autoimmune syndrome Autoimmune Polyendocrinopathy Syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (is_associated_with::APECED). Disruption of AIRE results in the development of a range of autoimmune diseases, the most common clinical conditions in the syndrome are is_associated_with::hypoparathyroidism, primary adrenocortical failure and is_associated_with::chronic mucocutaneous candidiasis.

A gene knockout of the murine homolog Aire has created a transgenic mouse model to study the mechanism of disease in human patients.

Interactions
Autoimmune regulator has been shown to interact with is_associated_with::CREB binding protein.