Aire.
Mutations in the transcriptional regulator, Aire, cause APECED, a polyglandular autoimmune disease with monogenic transmission. Animal models of APECED have revealed that Aire plays an important role in T cell tolerance induction in the thymus, mainly by promoting ectopic expression of a large repertoire of transcripts encoding proteins normally restricted to differentiated organs residing in the periphery. The absence of Aire results in impaired clonal deletion of self-reactive thymocytes, which escape into the periphery and attack a variety of organs. In addition, Aire is a proapoptotic factor, expressed at the final maturation stage of thymic medullary epithelial cells, a function that may promote cross-presentation of the antigens encoded by Aire-induced transcripts in these cells. Transcriptional regulation by Aire is unusual in being very broad, context-dependent, probabilistic, and noisy. Structure/function analyses and identification of its interaction partners suggest that Aire may impact transcription at several levels, including nucleosome displacement during elongation and transcript splicing or other aspects of maturation.
Mathis
Diane
D
Section on Immunology and Immunogenetics, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital; Harvard Medical School; and the Harvard Stem Cell Institute, Boston, Massachusetts 02215, USA. cbdm@joslin.harvard.edu
Benoist
Christophe
C
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein