Research Article

Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein

Science  15 Nov 2002:
Vol. 298, Issue 5597, pp. 1395-1401
DOI: 10.1126/science.1075958

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Abstract

Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue– restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed “central” tolerance in controlling autoimmunity.

  • * To whom correspondence should be addressed. E-mail: cbdm{at}joslin.harvard.edu

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