Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein-Reference-Cited by-同舟云学术

Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein

Published:2002-11-15 Issue:5597 Volume:298 Page:1395-1401
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Anderson Mark S.¹,Venanzi Emily S.¹,Klein Ludger²,Chen Zhibin¹,Berzins Stuart P.¹,Turley Shannon J.¹,von Boehmer Harald²,Bronson Roderick³,Dierich Andrée⁴,Benoist Christophe¹,Mathis Diane¹

Affiliation:

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.

2. Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

3. Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

4. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 rue Laurent Fries, 67404 Strasbourg, France.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference40 articles.

1. Garza K. M., Chan V. S., Ohashi P. S., Rev. Immunogenet. 2, 2 (2000).

2. Peripheral-antigen-expressing cells in thymic medulla: factors in self-tolerance and autoimmunity

3. Self-antigen presentation by thymic stromal cells: a subtle division of labor

4. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self

5. Sampling of complementing self-antigen pools by thymic stromal cells maximizes the scope of central T cell tolerance

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