Autoimmune regulator

"AIRE" redirects here. For other uses, see Aire.

Autoimmune regulator
PDB rendering based on 1xwh.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1XWH, 2KE1, 2KFT, 2LRI
Identifiers
Symbols	AIRE ; AIRE1; APECED; APS1; APSI; PGA1
External IDs	OMIM: 607358 MGI: 1338803 HomoloGene: 327 GeneCards: AIRE Gene
Gene ontology Molecular function • RNA polymerase II regulatory region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • chromatin binding • protein binding • zinc ion binding • histone binding • identical protein binding • transcription regulatory region DNA binding • translation regulator activity Cellular component • nucleus • cytoplasm Biological process • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • regulation of translation • immune response • humoral immune response • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	326	11634
Ensembl	ENSG00000160224	ENSMUSG00000000731
UniProt	O43918	Q9Z0E3
RefSeq (mRNA)	NM_000383	NM_001271549
RefSeq (protein)	NP_000374	NP_001258478
Location (UCSC)	Chr 21: 44.29 – 44.3 Mb	Chr 10: 78.03 – 78.04 Mb
PubMed search	[1]	[2]

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

Each 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 (mTEC) express major proteins from elsewhere in the body (so called "tissue-restricted antigens" - TRA), and T cells that respond to those proteins are eliminated through cell death(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 autoimmune disease.

Function

In the thymus, the autoimmune regulator causes transcription of a wide selection of organ-specific genes that create proteins that are usually only expressed in peripheral tissues, creating an "immunological self-shadow" in the thymus. It is important that self-reactive T cells that bind strongly to self-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 autoimmunity later on by allowing for the elimination of auto-reactive 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 TRAs 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 insulin, in the thymus. This expression then allows maturing 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 (APECED). Disruption of AIRE results in the development of a range of autoimmune diseases, the most common clinical conditions in the syndrome are hypoparathyroidism, primary adrenocortical failure and 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 CREB binding protein.

See also

• List of human clusters of differentiation for a list of CD molecules
• Immune system
• Immune tolerance

External links

• AIRE protein at the US National Library of Medicine Medical Subject Headings (MeSH)