Control of central and peripheral tolerance by Aire

Authors


Mark S. Anderson
UCSF Diabetes Center
513 Parnassus Ave. HSW 1114, Box 0540
San Francisco, CA 94143, USA
Tel.: +1 415 502 8052
Fax: +1 415 564 5813
e-mail: manderson@diabetes.ucsf.edu

Abstract

Summary:  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.

Ancillary