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Critical Reviews™ in Immunology
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ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v31.i3.10
pages 171-187

The Contribution of Thymic Stromal Abnormalities to Autoimmune Disease

Anne L. Fletcher
Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Australia; and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Adrienne Calder
Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Australia
Melanie N. Hince
Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Australia
Richard L. Boyd
Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Australia
Ann P. Chidgey
Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Australia

SINOPSIS

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.


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