Autoimmune regulator

AIRE
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2LRI, 1XWH, 2KE1, 2KFT
Identifiers
Aliases	AIRE, AIRE1, APECED, APS1, APSI, PGA1, autoimmune regulator
External IDs	OMIM: 607358 MGI: 1338803 HomoloGene: 327 GeneCards: AIRE
Gene location (Human)
Chr.	Chromosome 21 (human)
End	44,298,648 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	77,879,444 bp
RNA expression pattern
	Top expressed in
	hypothalamus; ; cingulate gyrus; ; lymph node; ; nucleus accumbens; ; substantia nigra; ; dorsolateral prefrontal cortex; ; Brodmann area 9; ; caudate nucleus; ; putamen; ; urethra;
	Top expressed in
	urethra; ; thymus; ; secondary oocyte; ; parasympathetic nervous system; ; pharynx; ; saccule; ; cumulus cell; ; ectoderm; ; thyroid gland; ; surface ectoderm;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	DNA binding; RNA polymerase II transcription regulatory region sequence-specific DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; histone binding; chromatin binding; transcription coregulator activity; translation regulator activity; metal ion binding; protein binding; identical protein binding; zinc ion binding; DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	cytoplasm; intracellular anatomical structure; nuclear body; nucleus;
Biological process	regulation of transcription, DNA-templated; transcription, DNA-templated; negative thymic T cell selection; humoral immune response; immune response; regulation of translation; positive regulation of transcription by RNA polymerase II; transcription by RNA polymerase II; peripheral T cell tolerance induction; central tolerance induction to self antigen; chemokine production; positive regulation of transcription, DNA-templated; thymus epithelium morphogenesis; regulation of thymocyte migration;
	Sources:Amigo / QuickGO
Orthologs
	326
	11634
	ENSG00000160224
	ENSMUSG00000000731
	O43918
	Q9Z0E3
	NM_000383; NM_000658; NM_000659
NM_001271549; NM_001271550; NM_001271551; NM_001271552; NM_001271553;
	NM_001271554; NM_001271555; NM_001271556; NM_001271557; NM_001271558; NM_001271559; NM_009646
	NP_000374
NP_001258478; NP_001258479; NP_001258480; NP_001258481; NP_001258482;
	NP_001258483; NP_001258484; NP_001258485; NP_001258486; NP_001258487; NP_001258488; NP_033776
	Wikidata
View/Edit Human	View/Edit Mouse

The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. It is a 13kb gene on chromosome 21q22.3 that has 545 amino acids. AIRE is a transcription factor expressed in the medulla (inner part) of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed.

Each T cell recognizes a specific antigen when it is presented in complex with a major histocompatibility complex (MHC) molecule by an antigen presenting cell. This recognition is accomplished by the T cell receptors expressed on the cell surface. T cells receptors are generated by randomly shuffled gene segments which results in a highly diverse population of T cells—each with a unique antigen specificity. Subsequently, T cells with receptors that recognize the body's own proteins need to be eliminated while still in the thymus. Through the action of AIRE, 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 AIRE drives negative selection of self-recognizing T cells. When AIRE is defective, T cells that recognize antigens normally produced by the body can exit the thymus and enter circulation. This can result in a variety of autoimmune diseases.

The gene was first reported by two independent research groups Aaltonen et al. and Nagamine et al. in 1997 who were able to isolate and clone the gene from human chromosome 21q22.3. Their work was able to show that mutations in the AIRE gene are responsible for the pathogenesis of Autoimmune polyglandular syndrome type I. More insight into the AIRE protein was later provided by Heino et al. in 2000. They showed that AIRE protein is mainly expressed in the thymic medullary epithelial cells using immunohistochemistry.

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