[Central tolerance and autoimmune diseases].
Central tolerance is established by the repertoire selection of immature T lymphocytes in the thymus, avoiding autoimmune responses to self-antigens. Differential ligand-TCR interactions that result in positive and negative selection initiate differential intracellular signals that, in turn, lead to the survival-or-death decision of immature thymocytes. TCR signal dysregulation due to the mutation of ZAP-70 or defective apoptosis of autoreactive thymocytes due to the deficiency of pro-apoptotic protein Bim impair tolerance and cause autoimmunity. Thymic repertoire selection also induces the development of CD25(+)CD4(+) regulatory T cells, which play important roles for maintaining peripheral tolerance. Furthermore, the establishment of central tolerance requires the development of thymic medulla that is mediated by the activation of NF-kappaB signaling pathway, promiscuous expression of tissue-specific self-antigens by medullary epithelial cells that is regulated by AIRE, and cortex-to-medulla migration of developing thymocytes that is regulated by CCR7-mediated chemokine signals.
Nitta
Takeshi
T
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima.
Takahama
Yousuke
Y
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D006801:Humans; D007108:Immune Tolerance; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D000096927:AIRE Protein
D051017:Apoptosis Regulatory Proteins; D014157:Transcription Factors; D000096927:AIRE Protein