Control of central and peripheral tolerance by Aire

Immunol Rev. 2011 May;241(1):89-103. doi: 10.1111/j.1600-065X.2011.01008.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIRE Protein
  • Animals
  • Autoantigens / immunology*
  • Autoimmunity
  • Clonal Deletion
  • Humans
  • Immune System / embryology
  • Immune System / growth & development
  • Immune System / immunology*
  • Immune Tolerance*
  • Mice
  • Mice, Transgenic
  • Organ Specificity
  • Thymus Gland / immunology*
  • Transcription Factors / immunology*

Substances

  • Autoantigens
  • Transcription Factors