Literature DB >> 12376594

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

Mark S Anderson1, Emily S Venanzi, Ludger Klein, Zhibin Chen, Stuart P Berzins, Shannon J Turley, Harald von Boehmer, Roderick Bronson, Andrée Dierich, Christophe Benoist, Diane Mathis.   

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.

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Year:  2002        PMID： 12376594     DOI： 10.1126/science.1075958

Source DB:  PubMed          Journal:  Science        ISSN： 0036-8075            Impact factor:   47.728


  803 in total

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