Journal
IMMUNOLOGICAL REVIEWS
Volume 241, Issue -, Pages 89-103Publisher
WILEY
DOI: 10.1111/j.1600-065X.2011.01008.x
Keywords
autoimmunity; transcriptional activator; thymic selection; peripheral tolerance
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Funding
- JDRF
- NIH
- Helmsley Foundation
- Burroughs Wellcome
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The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined.
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