title: [Function of Aire in central and peripheral immune tolerance].
abstract: Negative selection induces central tolerance in which self-reactive T cells are deleted by medullary thymic epithelial cells (mTECs) to prevent autoimmunity. The transcriptional factor, autoimmune regulator (Aire), controls the expression of tissue-specific antigens (TSAs) by mTECs for negative selection. The mechanisms by which Aire targets loci which encode TSAs are unknown in detail; recently, however, the ATF7ip-MBD1 complex was identified as an Aire-interacting transcriptional protein complex required for its targeting the loci. Lineage tracing of Aire(+) mTECs identified that mTECs have a post-Aire stage during the development, where they lost maturation markers but maintained intermediate TSA expression, and Aire is required for the terminal differentiation of mTEC's. Extrathymic Aire-expressing cells (eTACs) are identified in murine and human secondary lymphoid organs. eTACs express major histocompatibility complex class II(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell population, which is distinct from mTECs and dendritic cells. They can induce activation-induced cell death of self-reactive CD8(+) T cells and unresponsiveness of self-reactive CD4(+) T cells through a mechanism that does not require regulatory T cells, suggesting that peripheral Aire plays a complementary role for central tolerance.
authors: Postdoctoral Fellow, Laboratory of Dr. Mark S Anderson, Diabetes Center, University of California, San Francisco.
authors: Takaaki
authors: T
authors: Hanafusa
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016923:Cell Death; D006801:Humans; D007108:Immune Tolerance; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein