Autoimmune regulator


Autoimmune regulator

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.OMIM. [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=240300] ] 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.cite journal | author = Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kämpe O, Eskelin P, Pelto-Huikko M, Peltonen L | title = Aire deficient mice develop multiple features of APECED phenotype and show altered immune response | journal = Hum. Mol. Genet. | volume = 11 | issue = 4 | pages = 397–409 | year = 2002 | pmid = 11854172 | doi = 10.1093/hmg/11.4.397 | issn = ]

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.cite journal | author = Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D | title = Projection of an immunological self shadow within the thymus by the aire protein | journal = Science | volume = 298 | issue = 5597 | pages = 1395–401 | year = 2002 | pmid = 12376594 | doi = 10.1126/science.1075958 | issn = ] This expression then allows maturing thymocytes to become tolerant towards peripheral organs, thereby suppressing autoimmune disease.cite journal | author = Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC | title = Aire regulates negative selection of organ-specific T cells | journal = Nat. Immunol. | volume = 4 | issue = 4 | pages = 350–4 | year = 2003 | pmid = 12612579 | doi = 10.1038/ni906 | issn = ]

ee also

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

References

Further reading

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citations =
*cite journal | author=Björses P, Aaltonen J, Horelli-Kuitunen N, "et al." |title=Gene defect behind APECED: a new clue to autoimmunity. |journal=Hum. Mol. Genet. |volume=7 |issue= 10 |pages= 1547–53 |year= 1998 |pmid= 9735375 |doi=
*cite journal | author=Heino M, Peterson P, Kudoh J, "et al." |title=APECED mutations in the autoimmune regulator (AIRE) gene. |journal=Hum. Mutat. |volume=18 |issue= 3 |pages= 205–11 |year= 2001 |pmid= 11524731 |doi= 10.1002/humu.1176
*cite journal | author=Sato K, Nakajima K, Imamura H, "et al." |title=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. |journal=Endocr. J. |volume=49 |issue= 6 |pages= 625–33 |year= 2003 |pmid= 12625412 |doi=
*cite journal | author=Ruan QG, She JX |title=Autoimmune polyglandular syndrome type 1 and the autoimmune regulator. |journal=Clin. Lab. Med. |volume=24 |issue= 1 |pages= 305–17 |year= 2004 |pmid= 15157567 |doi= 10.1016/j.cll.2004.01.008
*cite journal | author=Holmdahl R |title=Aire-ing self antigen variability and tolerance. |journal=Eur. J. Immunol. |volume=37 |issue= 3 |pages= 598–601 |year= 2007 |pmid= 17323409 |doi= 10.1002/eji.200737152
*cite journal | author=Aaltonen J, Björses P, Sandkuijl L, "et al." |title=An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. |journal=Nat. Genet. |volume=8 |issue= 1 |pages= 83–7 |year= 1995 |pmid= 7987397 |doi= 10.1038/ng0994-83
*cite journal | author=Aaltonen J, Horelli-Kuitunen N, Fan JB, "et al." |title=High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH. |journal=Genome Res. |volume=7 |issue= 8 |pages= 820–9 |year= 1997 |pmid= 9267805 |doi=
*cite journal | author=Nagamine K, Peterson P, Scott HS, "et al." |title=Positional cloning of the APECED gene. |journal=Nat. Genet. |volume=17 |issue= 4 |pages= 393–8 |year= 1997 |pmid= 9398839 |doi= 10.1038/ng1297-393
*cite journal | author= |title=An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. |journal=Nat. Genet. |volume=17 |issue= 4 |pages= 399–403 |year= 1997 |pmid= 9398840 |doi= 10.1038/ng1297-399
*cite journal | author=Scott HS, Heino M, Peterson P, "et al." |title=Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins. |journal=Mol. Endocrinol. |volume=12 |issue= 8 |pages= 1112–9 |year= 1998 |pmid= 9717837 |doi=
*cite journal | author=Heino M, Scott HS, Chen Q, "et al." |title=Mutation analyses of North American APS-1 patients. |journal=Hum. Mutat. |volume=13 |issue= 1 |pages= 69–74 |year= 1999 |pmid= 9888391 |doi= 10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6 |doilabel=10.1002/(SICI)1098-1004(1999)13:169::AID-HUMU83.0.CO;2-6
*cite journal | author=Björses P, Pelto-Huikko M, Kaukonen J, "et al." |title=Localization of the APECED protein in distinct nuclear structures. |journal=Hum. Mol. Genet. |volume=8 |issue= 2 |pages= 259–66 |year= 1999 |pmid= 9931333 |doi=
*cite journal | author=Rinderle C, Christensen HM, Schweiger S, "et al." |title=AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered sub-cellular distribution of mutants lacking the PHD zinc fingers. |journal=Hum. Mol. Genet. |volume=8 |issue= 2 |pages= 277–90 |year= 1999 |pmid= 9931335 |doi=
*cite journal | author=Björses P, Halonen M, Palvimo JJ, "et al." |title=Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. |journal=Am. J. Hum. Genet. |volume=66 |issue= 2 |pages= 378–92 |year= 2000 |pmid= 10677297 |doi=
*cite journal | author=Pitkänen J, Doucas V, Sternsdorf T, "et al." |title=The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein. |journal=J. Biol. Chem. |volume=275 |issue= 22 |pages= 16802–9 |year= 2000 |pmid= 10748110 |doi= 10.1074/jbc.M908944199
*cite journal | author=Hattori M, Fujiyama A, Taylor TD, "et al." |title=The DNA sequence of human chromosome 21. |journal=Nature |volume=405 |issue= 6784 |pages= 311–9 |year= 2000 |pmid= 10830953 |doi= 10.1038/35012518
*cite journal | author=Pitkänen J, Vähämurto P, Krohn K, Peterson P |title=Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain. |journal=J. Biol. Chem. |volume=276 |issue= 22 |pages= 19597–602 |year= 2001 |pmid= 11274163 |doi= 10.1074/jbc.M008322200
*cite journal | author=Saugier-Veber P, Drouot N, Wolf LM, "et al." |title=Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. |journal=Eur. J. Endocrinol. |volume=144 |issue= 4 |pages= 347–51 |year= 2001 |pmid= 11275943 |doi=

External links

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Look at other dictionaries:

  • Autoimmune polyendocrinopathy syndrome — A genetic autoimmune disease with an extraordinary array of clinical features but characterized most often by at least 2 of the following 3 findings: hypoparathyroidism underfunction of the parathyroid glands which control calcium, candidiasis… …   Medical dictionary

  • Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) — A genetic autoimmune disease with an extraordinary array of clinical features but characterized most often by at least 2 of the following 3 findings: hypoparathyroidism underfunction of the parathyroid glands which control calcium, candidiasis… …   Medical dictionary

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  • APECED (autoimmune polyendocrinopathy) — 1. The child with APS develops problems in numerous glands (polyglandular) including hypoparathyroidism, hypogonadism (with sex gland failure), adrenal insufficiency, type 1 (insulin dependent) diabetes with insufficient insulin production by the …   Medical dictionary

  • Polyendocrinopathy syndrome, autoimmune — A genetic autoimmune disease with an extraordinary array of clinical features but characterized most often by at least 2 of the following 3 findings: hypoparathyroidism underfunction of the parathyroid glands which control calcium, candidiasis… …   Medical dictionary

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  • polyendocrine autoimmune syndromes — polyglandular autoimmune syndromes syndromes comprising combinations of endocrine and nonendocrine autoimmune diseases. Type I is caused by mutations in the autoimmune regulator gene (AIRE, locus: 21q22.3) and occurs in infants and children. It… …   Medical dictionary

  • APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) — A genetic autoimmune disease with an extraordinary array of clinical features but characterized most often by at least 2 of the following 3 findings: hypoparathyroidism underfunction of the parathyroid glands which control calcium, candidiasis… …   Medical dictionary

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