Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein
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.
- Publication:
-
Science
- Pub Date:
- November 2002
- DOI:
- 10.1126/science.1075958
- Bibcode:
- 2002Sci...298.1395A
- Keywords:
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- IMMUNOLOGY