title: Control of central and peripheral tolerance by Aire.
abstract: 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.
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Metzger
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D017637:Clonal Deletion; D006801:Humans; D007107:Immune System / Q000196:embryology / Q000254:growth & development / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D013950:Thymus Gland / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D000096927:AIRE Protein
chemical_list: D001324:Autoantigens; D014157:Transcription Factors; D000096927:AIRE Protein