Death in the AIRE.
When thymic epithelia begin to synthesize peripheral tissue antigens such as insulin, we are seeing the result of autoimmune regulator (AIRE) activity and the workings of central tolerance. AIRE is an extraordinary protein that repatterns the transcriptome of medullary thymic epithelia (mTECs) to produce a stroma decorated with peripheral self-peptides. These peptidic arrays are used to purge self-reactive T cells, thereby averting autoimmunity. We now propose that an inherently cytotoxic event such as global chromatin modification paves the way for AIRE action. This injury stimulus might impose temporal restrictions for the T-cell education process and is endured, at least transiently, by the unique cellular environment provided by the medullary thymic epithelia.
Department of Pathology, Divisions of Immunology and Cellular Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Brian J
BJ
Ferguson
Anne
A
Cooke
Pärt
P
Peterson
Tina
T
Rich
D000818:Animals; D050882:CREB-Binding Protein / Q000502:physiology; D016923:Cell Death; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D007108:Immune Tolerance; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D000096927:AIRE Protein
D050882:CREB-Binding Protein; D014157:Transcription Factors; D000096927:AIRE Protein