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Autoimmune regulator


Autoimmune Regulator
Identifiers
Symbol AIRE
Alt. Symbols AIRE1, APECED, APS1, APSI, PGA1
Entrez 326
HUGO 360
OMIM *607358
RefSeq NM_000383.1
UniProt CAA08759
Other data
Locus Chr. 21 q22.3

The Autoimmune Regulator, abbreviated AIRE, is a human gene which is expressed in the thymus. It causes transcription of a wide selection of organ-specific genes. This reduces the threat of autoimmunity occurring by allowing the elimination of autoreactive T cells by the process of negative selection if they are too reactive to self.

It 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.[1] AIRE is expressed primarily in the thymus.

A gene knockout of the murine homolog Aire has created a transgenic mouse model to study the mechanism of disease in human patients.[2] Research on the knockout mouse has demonstrated that Aire functions through initiating the transcription of a diverse set of self-antigens, such as insulin, in the thymus.[3] This expression then allows maturing thymocytes to become tolerant towards peripheral organs, thereby suppressing autoimmune disease.[4]

References

  1. ^ OMIM. [1]
  2. ^ Ramsey, C. et al. (2002) Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet 11 (4), 397-409.
  3. ^ Anderson, M.S. et al. (2002) Projection of an Immunological Self-Shadow Within the Thymus by the Aire Protein. Science 298 (5597), 1395-1401
  4. ^ Liston, A. et al. (2003) Aire regulates negative selection of organ-specific T cells. Nat Immunol 4 (4), 350-354

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