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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.
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Pugliese, A., Zeller, M., Fernandez, A., Zalcberg, L. J., Bartlett, R. J., Ricordi, C., Pietropaolo, M., Eisenbarth, G. S., Bennett, S. T., & Patel, D. D. (1997) · Nature Genetics · doi:10.1038/ng0397-293 · Cited by 945
Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus
Vafiadis, P., Bennett, S. T., Todd, J. A., Nadeau, J., Grabs, R., Goodyer, C. G., Wickramasinghe, S., Colle, E., & Polychronakos, C. (1997) · Nature Genetics · doi:10.1038/ng0397-289 · Cited by 809
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Metadata
- Authors
- 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.
- Venue
- Science
- Published
- 2002-11-15
- Volume
- 298
- Issue
- 5597
- Pages
- 1395-1401
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2165214298
- Cited by
- 2,486
- References
- 2
- FWCI
- 32.70
- Type
- journal article
- Language
- en
- Open access
- closed
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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. https://doi.org/10.1126/science.1075958
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