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Autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)

PDB rendering based on 1xwh.
Available structures
External IDs OMIM607358 MGI1338803 HomoloGene327 GeneCards: AIRE Gene
RNA expression pattern
PBB GE AIRE 208090 s at tn.png
More reference expression data
Species Human Mouse
Entrez 326 11634
Ensembl ENSG00000160224 ENSMUSG00000000731
UniProt O43918 Q3ZB65
RefSeq (mRNA) NM_000383 NM_009646
RefSeq (protein) NP_000374 NP_033776
Location (UCSC) Chr 21:
44.53 - 44.54 Mb
Chr 10:
77.43 - 77.45 Mb
PubMed search [2] [3]

The Autoimmune Regulator, abbreviated AIRE, is a human transcription factor expressed in the medulla of the thymus and is important in the prevention of autoimmune disease.



In the thymus it causes transcription of a wide selection of organ-specific genes which create proteins that are usually only expressed in peripheral tissues, creating an "immunological self-shadow" in the thymus.[1][2] It is important that self-reactive T cells which 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 autoimmunity occurring later on by allowing for the elimination of auto-reactive T cells which bind antigens not traditionally found in the thymus.

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]

The AIRE gene is expressed in many other tissues as well.[5]


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.[6]

A gene knockout of the murine homolog Aire has created a transgenic mouse model to study the mechanism of disease in human patients.[7]


Autoimmune regulator has been shown to interact with CREB binding protein.[8][9]

See also


  1. ^ Anderson, M.S. et al. (2002) Projection of an Immunological Self-Shadow Within the Thymus by the Aire Protein. Science 298 (5597), 1395-1401
  2. ^ Liston, A. et al. (2003) Aire regulates negative selection of organ-specific T cells. Nat Immunol 4 (4), 350-354
  3. ^ Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D (2002). "Projection of an immunological self shadow within the thymus by the aire protein". Science 298 (5597): 1395–401. doi:10.1126/science.1075958. PMID 12376594.  
  4. ^ Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC (2003). "Aire regulates negative selection of organ-specific T cells". Nat. Immunol. 4 (4): 350–4. doi:10.1038/ni906. PMID 12612579.  
  5. ^ BioGPS > AIRE > Gene expression/activity chart Retrieved on Dec 19, 2009
  6. ^ OMIM. [1]
  7. ^ Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kämpe O, Eskelin P, Pelto-Huikko M, Peltonen L (2002). "Aire deficient mice develop multiple features of APECED phenotype and show altered immune response". Hum. Mol. Genet. 11 (4): 397–409. doi:10.1093/hmg/11.4.397. PMID 11854172.  
  8. ^ Pitkänen, J; Doucas V, Sternsdorf T, Nakajima T, Aratani S, Jensen K, Will H, Vähämurto P, Ollila J, Vihinen M, Scott H S, Antonarakis S E, Kudoh J, Shimizu N, Krohn K, Peterson P (Jun. 2000). "The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein". J. Biol. Chem. (UNITED STATES) 275 (22): 16802–9. doi:10.1074/jbc.M908944199. ISSN 0021-9258. PMID 10748110.  
  9. ^ Iioka, Takashi; Furukawa Keizo, Yamaguchi Akira, Shindo Hiroyuki, Yamashita Shunichi, Tsukazaki Tomoo (Aug. 2003). "P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain". J. Bone Miner. Res. (United States) 18 (8): 1419–29. ISSN 0884-0431. PMID 12929931.  

Further reading

  • Björses P, Aaltonen J, Horelli-Kuitunen N, et al. (1998). "Gene defect behind APECED: a new clue to autoimmunity.". Hum. Mol. Genet. 7 (10): 1547–53. doi:10.1093/hmg/7.10.1547. PMID 9735375.  
  • Heino M, Peterson P, Kudoh J, et al. (2001). "APECED mutations in the autoimmune regulator (AIRE) gene.". Hum. Mutat. 18 (3): 205–11. doi:10.1002/humu.1176. PMID 11524731.  
  • Sato K, Nakajima K, Imamura H, et al. (2003). "A novel missense mutation of AIRE gene in a patient with autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), accompanied with progressive muscular atrophy: case report and review of the literature in Japan.". Endocr. J. 49 (6): 625–33. doi:10.1507/endocrj.49.625. PMID 12625412.  
  • Ruan QG, She JX (2004). "Autoimmune polyglandular syndrome type 1 and the autoimmune regulator.". Clin. Lab. Med. 24 (1): 305–17. doi:10.1016/j.cll.2004.01.008. PMID 15157567.  
  • Holmdahl R (2007). "Aire-ing self antigen variability and tolerance.". Eur. J. Immunol. 37 (3): 598–601. doi:10.1002/eji.200737152. PMID 17323409.  
  • Aaltonen J, Björses P, Sandkuijl L, et al. (1995). "An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21.". Nat. Genet. 8 (1): 83–7. doi:10.1038/ng0994-83. PMID 7987397.  
  • Aaltonen J, Horelli-Kuitunen N, Fan JB, et al. (1997). "High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH.". Genome Res. 7 (8): 820–9. PMID 9267805.  
  • Nagamine K, Peterson P, Scott HS, et al. (1997). "Positional cloning of the APECED gene.". Nat. Genet. 17 (4): 393–8. doi:10.1038/ng1297-393. PMID 9398839.  
  • Aaltonen, Johanna (1997). "An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains.". Nat. Genet. 17 (4): 399–403. doi:10.1038/ng1297-399. PMID 9398840.  
  • Scott HS, Heino M, Peterson P, et al. (1998). "Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.". Mol. Endocrinol. 12 (8): 1112–9. doi:10.1210/me.12.8.1112. PMID 9717837.  
  • Heino M, Scott HS, Chen Q, et al. (1999). "Mutation analyses of North American APS-1 patients.". Hum. Mutat. 13 (1): 69–74. doi:10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6. PMID 9888391.  
  • Björses P, Pelto-Huikko M, Kaukonen J, et al. (1999). "Localization of the APECED protein in distinct nuclear structures.". Hum. Mol. Genet. 8 (2): 259–66. doi:10.1093/hmg/8.2.259. PMID 9931333.  
  • Rinderle C, Christensen HM, Schweiger S, et al. (1999). "AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered sub-cellular distribution of mutants lacking the PHD zinc fingers.". Hum. Mol. Genet. 8 (2): 277–90. doi:10.1093/hmg/8.2.277. PMID 9931335.  
  • Björses P, Halonen M, Palvimo JJ, et al. (2000). "Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein.". Am. J. Hum. Genet. 66 (2): 378–92. doi:10.1086/302765. PMID 10677297.  
  • Pitkänen J, Doucas V, Sternsdorf T, et al. (2000). "The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein.". J. Biol. Chem. 275 (22): 16802–9. doi:10.1074/jbc.M908944199. PMID 10748110.  
  • Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21.". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.  
  • Pitkänen J, Vähämurto P, Krohn K, Peterson P (2001). "Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain.". J. Biol. Chem. 276 (22): 19597–602. doi:10.1074/jbc.M008322200. PMID 11274163.  
  • Saugier-Veber P, Drouot N, Wolf LM, et al. (2001). "Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.". Eur. J. Endocrinol. 144 (4): 347–51. doi:10.1530/eje.0.1440347. PMID 11275943.  

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