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

2146 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.",

author = "Anderson, \{Mark S.\} and Venanzi, \{Emily S.\} and Ludger Klein and Zhibin Chen and Berzins, \{Stuart P.\} and Turley, \{Shannon J.\} and \{Von Boehmer\}, Harald and Roderick Bronson and Andr{\'e}e Dierich and Christophe Benoist and Diane Mathis",

year = "2002",

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doi = "10.1126/science.1075958",

language = "English",

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TY - JOUR

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.

UR - https://www.scopus.com/pages/publications/0037112047

U2 - 10.1126/science.1075958

DO - 10.1126/science.1075958

M3 - Article

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AN - SCOPUS:0037112047

SN - 0036-8075

VL - 298

SP - 1395

EP - 1401

JO - Science

JF - Science

IS - 5597

ER -

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

Abstract

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