Autoimmune regulator

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AIRE
AIRE
according to PDB  1xwh
other names

APECED protein

Existing structure data : 1XWH , 2KE1 , 2KFT , 2LRI

Properties of human protein
Mass / length primary structure 57.7 kilodaltons / 545 amino acids (isoform 1 / AIRE-1)

35.7 kilodaltons / 338 amino acids (isoform 2 / AIRE-2)
25.9 kilodaltons / 244 amino acids (isoform 3 / AIRE-3)
36.5 kilodaltons / 348 amino acids (isoform 4)

Isoforms 4th
Identifier
Gene names AIRE APECED
External IDs
Orthologue
human House mouse
Entrez 326 11634
Ensemble ENSG00000160224 ENSMUSG00000000731
UniProt O43918 Q9Z0E3
Refseq (mRNA) NM_000383 NM_001271549
Refseq (protein) NP_000374 NP_001258478
Gene locus Chr 21: 44.29 - 44.3 Mb Chr 10: 78.03 - 78.04 Mb
PubMed search 326 11634

The protein autoimmune regulator ( AIRE ) is a transcription factor that helps prevent autoimmunity in the formation of T cells .

properties

AIRE is formed at the transition from the cortex to the medulla of the thymus in epithelial cells (mTEC, from English medullary thymic epithelial cells ). The mTEC are CD45-negative , CD40 -, CD80 - and PD-L1 -positive, EpCAM-positive, Ly51 positive cytokeratin-5-positive and cytokeratin 14 positive. AIRE binds to the CREB binding protein . As a transcription factor, AIRE also induces the gene expression of several thousand different tissue-specific autoantigens , which after degradation in the proteasome are transported via the TAP translocase into the endoplasmic reticulum , where they bind to MHCI proteins . The autoantigens are exocytosed to the cell surface from the endoplasmic reticulum . The autoantigens are bound to MHCI proteins and presented on the cell surface. If the resulting T cells bind to it, apoptosis is triggered in these autoreactive T cells (negative selection). As a result, AIRE is involved in the development of a central immune tolerance to autoantigens. If the negative selection is incorrect, T-cell-based autoimmune diseases can develop. Furthermore, AIRE induces the formation of regulatory T cells that contribute to peripheral immune tolerance.

A genetic defect in the AIRE gene is involved in the development of the autoimmune disease APECED .

Individual evidence

  1. ^ R. Perniola, G. Musco: The biophysical and biochemical properties of the autoimmune regulator (AIRE) protein. In: Biochimica et Biophysica Acta . Volume 1842, number 2, February 2014, ISSN  0006-3002 , pp. 326-337, doi: 10.1016 / j.bbadis.2013.11.020 , PMID 24275490 .
  2. ↑ FX Hubert, SA Kinkel, KE Webster, P. Cannon, PE Crewther, AI Proeitto, L. Wu, WR Heath, HS Scott: A specific anti-Aire antibody reveals aire expression is restricted to medullary thymic epithelial cells and not expressed in periphery. In: Journal of Immunology (Baltimore, Md.: 1950). Volume 180, Number 6, March 2008, ISSN  0022-1767 , pp. 3824-3832, PMID 18322189 .
  3. ↑ a b M. S. Anderson, MA Su: Aire and T cell development. In: Current opinion in immunology. Volume 23, number 2, April 2011, ISSN  1879-0372 , pp. 198-206, doi: 10.1016 / j.coi.2010.11.007 , PMID 21163636 , PMC 3073725 (free full text).
  4. ↑ K. Zumer, K. Saksela, BM Peterlin: The mechanism of tissue-restricted antigen gene expression by AIRE. In: Journal of Immunology (Baltimore, Md.: 1950). Volume 190, Number 6, March 2013, ISSN  1550-6606 , pp. 2479-2482, doi: 10.4049 / jimmunol.1203210 , PMID 23456700 .
  5. ^ M. Laan, P. Peterson: The many faces of aire in central tolerance. In: Frontiers in immunology. Volume 4, 2013, ISSN  1664-3224 , p. 326, doi: 10.3389 / fimmu.2013.00326 , PMID 24130560 , PMC 3795325 (free full text).
  6. ↑ S. Yang, N. Fujikado, D. Kolodin, C. Benoist, D. Mathis: Regulatory T cells generated early in life play a distinct role in Maintaining self-tolerance. In: Science. 348, 2015, p. 589, doi: 10.1126 / science.aaa7017 .
  7. ^ Finnish-German APECED Consortium: An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. In: Nature genetics. Volume 17, Number 4, December 1997, ISSN  1061-4036 , pp. 399-403, doi: 10.1038 / ng1297-399 , PMID 9398840 .