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Central tolerance to self revealed by the autoimmune regulator
Author(s) -
Chan Alice Y.,
Anderson Mark S.
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12960
Subject(s) - autoimmune regulator , central tolerance , autoimmunity , biology , regulator , chromatin , transcription factor , microbiology and biotechnology , self tolerance , immunology , gene , regulation of gene expression , genetics , immune system
The autoimmune regulator (Aire) was initially identified as the gene causing multiorgan system autoimmunity in humans, and deletion of this gene in mice also resulted in organ‐specific autoimmunity. Aire regulates the expression of tissue‐specific antigens (TSAs) in medullary thymic epithelial cells (mTECs), which play a critical role in the negative selection of autoreactive T cells and the generation of regulatory T cells. More recently, the role of Aire in the development of mTECs has helped elucidate its ability to present the spectrum of TSAs needed to prevent autoimmunity. Molecular characterization of the functional domains of Aire has revealed multiple binding partners that assist Aire's function in altering gene transcription and chromatin remodeling. These recent advances have further highlighted the importance of Aire in central tolerance.