期刊
ANNUAL REVIEW OF IMMUNOLOGY
卷 27, 期 -, 页码 287-312出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.immunol.25.022106.141532
关键词
T cell tolerance; autoimmunity; thymus; transcription factor
类别
资金
- NIH [RO1 DK60027]
- William T Young Chair in Diabetes Research
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK060027] Funding Source: NIH RePORTER
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.
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