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

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Affiliations

  • 1. Section on Immunology and Immunogenetics, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital; Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA.
      Authors
    • Anderson MS 1
    (1 author)

ORCIDs linked to this article

Science, 10 Oct 2002, 298(5597):1395-1401
https://doi.org/10.1126/science.1075958 PMID: 12376594 

A comment on this article appears in "Immunology. Exposing thy self." Science. 2002 Nov 15;298(5597):1348-9.

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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Read article at publisher's site: https://doi.org/10.1126/science.1075958

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Funding 

Funders who supported this work.

NCI NIH HHS (1)

NIDDK NIH HHS (4)