title: The contribution of thymic stromal abnormalities to autoimmune disease.
abstract: In essence, normal thymus function involves the production of a broad repertoire of αβT cells capable of responding to foreign antigens with low risk of autoreactivity. Thymic epithelial cells are an essential component of the thymic stromal microenvironment, promoting the growth and export of self-tolerant thymocytes. Autoimmune disease, resulting from a loss of self-tolerance, is clinically and genetically complex, and accordingly has many potential etiological origins. However, it is commonly linked to defects in the thymic epithelial microenvironment. The study of autoimmune-linked thymic stromal dysfunction has indisputably advanced our understanding of T cell tolerance; notably, a field-wide paradigm shift occurred when autoimmune regulator (Aire) was found to drive expression of a multitude of peripheral tissue-restricted antigens in medullary thymic epithelial cells. Many other associations with polygenically controlled autoimmune diseases have been reported but are more difficult to definitively dissect. Paradoxically, immunodeficiency and age-related immunosenescence are also linked with increased autoimmunity. Here we discuss the theoretical basis and the evidence gathered thus far to support these associations.
authors: Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Australia. AnneL_Fletcher@dfci.harvard.edu
authors: Anne L
authors: AL
authors: Fletcher
authors: Adrienne
authors: A
authors: Calder
authors: Melanie N
authors: MN
authors: Hince
authors: Richard L
authors: RL
authors: Boyd
authors: Ann P
authors: AP
authors: Chidgey
mesh_terms: D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017634:Self Tolerance / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D000941:Antigens; D016207:Cytokines; D014157:Transcription Factors; D000096927:AIRE Protein