Projection of an immunological self shadow within the thymus by the aire protein

Mark S. Anderson, Emily S. Venanzi, Ludger Klein, Zhibin Chen, Stuart P. Berzins, Shannon J. Turley, Harald Von Boehmer, Roderick Bronson, Andrée Dierich, Christophe Benoist, Diane Mathis

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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.

Original languageEnglish (US)
Pages (from-to)1395-1401
Number of pages7
JournalScience
Volume298
Issue number5597
DOIs
StatePublished - Nov 15 2002

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Anderson, M. S., Venanzi, E. S., Klein, L., Chen, Z., Berzins, S. P., Turley, S. J., Von Boehmer, H., Bronson, R., Dierich, A., Benoist, C., & Mathis, D. (2002). Projection of an immunological self shadow within the thymus by the aire protein. Science, 298(5597), 1395-1401. https://doi.org/10.1126/science.1075958