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

doi:10.1126/science.1075958

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

Research output: Contribution to journal › Article › peer-review

2047 Scopus citations

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 language	English
Pages (from-to)	1395-1401
Number of pages	7
Journal	Science
Volume	298
Issue number	5597
DOIs	https://doi.org/10.1126/science.1075958
State	Published - 15 Nov 2002
Externally published	Yes

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title = "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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T1 - Projection of an immunological self shadow within the thymus by the aire protein

AU - Anderson, Mark S.

AU - Venanzi, Emily S.

AU - Klein, Ludger

AU - Chen, Zhibin

AU - Berzins, Stuart P.

AU - Turley, Shannon J.

AU - Von Boehmer, Harald

AU - Bronson, Roderick

AU - Dierich, Andrée

AU - Benoist, Christophe

AU - Mathis, Diane

PY - 2002/11/15

Y1 - 2002/11/15

N2 - 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.

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

Abstract

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