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

被引：1781

作者：

Anderson, MS

Venanzi, ES

Klein, L

Chen, ZB

Berzins, SP

Turley, SJ

von Boehmer, H

Bronson, R

Dierich, A

Benoist, C ^{[1
]}

Mathis, D

机构：

[1] Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Boston, MA 02115 USA

[5] ULP, CNRS, INSERM, Inst Genet & Biol Mol & Cellualire, F-67404 Strasbourg, France

来源：

SCIENCE | 2002年 / 298卷 / 5597期

关键词：

D O I：

10.1126/science.1075958

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 pro. le 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.

引用

页码：1395 / 1401

页数：8

共 39 条

[1] High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: Mechanisms of selection of the self-reactive repertoire [J].