Transcriptional regulation by AIRE: molecular mechanisms of central tolerance

被引：176

作者：

Peterson, Paert ^{[1
]}

Org, Tonis ^{[1
]}

Rebane, Ana ^{[1
]}

机构：

[1] Univ Tartu, Inst Gen & Mol Pathol, EE-50411 Tartu, Estonia

来源：

NATURE REVIEWS IMMUNOLOGY | 2008年 / 8卷 / 12期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/nri2450

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The negative selection of T cells in the thymus is necessary for the maintenance of self tolerance. Medullary thymic epithelial cells have a key function in this process as they express a large number of tissue-specific self antigens that are presented to developing T cells. Mutations in the autoimmune regulator (AIRE) protein cause a breakdown of central tolerance that is associated with decreased expression of self antigens in the thymus. In this Review, we discuss the role of AIRE in the thymus and recent advances in our understanding of how AIRE might function at the molecular level to regulate gene expression.

引用

页码：948 / 957

页数：10

共 137 条

[71] The autoimmune regulator (AIRE) is a DNA-binding protein [J].

Kumar, PG ;

Laloraya, M ;

Wang, CY ;

Ruan, QG ;

Davoodi-Semiromi, A ;

Kao, KJ ;

She, JX .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (44) :41357-41364

[72] Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of aire-deficient mice [J].

Kuroda, N ;

Mitani, T ;

Takeda, N ;

Ishimaru, N ;

Arakaki, R ;

Hayashi, Y ;

Bando, Y ;

Izumi, K ;

Takahashi, T ;

Nomura, T ;

Sakaguchi, S ;

Ueno, T ;

Takahama, Y ;

Uchida, D ;

Sun, SJ ;

Kajiura, F ;

Mouri, Y ;

Han, HW ;

Matsushima, A ;

Yamada, G ;

Matsumoto, M .

JOURNAL OF IMMUNOLOGY, 2005, 174 (04) :1862-1870

[73] A central role for central tolerance [J].

Kyewski, Bruno ;

Klein, Ludger .

ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :571-606

[74] Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self [J].

Lee, Je-Wook ;

Epardaud, Mathieu ;

Sun, Jing ;

Becker, Jessica E. ;

Cheng, Alexander C. ;

Yonekura, Ai-ris ;

Heath, Joan K. ;

Turley, Shannon J. .

NATURE IMMUNOLOGY, 2007, 8 (02) :181-190

[75] Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice [J].

Li, Juan ;

Li, Yan ;

Yao, Jin-Yan ;

Jin, Rong ;

Zhu, Ming-Zhao ;

Qian, Xiao-Ping ;

Zhang, Jun ;

Fu, Yang-Xin ;

Wu, Li ;

Zhang, Yu ;

Chen, Wei-Feng .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (46) :18175-18180

[76] DNA-PK contributes to the phosphorylation of AIRE: Importance in transcriptional activity [J].

Liiv, Ingrid ;

Rebane, Ana ;

Org, Tonis ;

Saare, Mario ;

Maslovskaja, Julia ;

Kisand, Kai ;

Juronen, Erkki ;

Valmu, Leena ;

Bottomley, Matthew James ;

Kalkkinen, Nisse ;

Peterson, Part .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2008, 1783 (01) :74-83

[77] Gene dosage-limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity [J].

Liston, A ;

Gray, DHD ;

Lesage, S ;

Fletcher, AL ;

Wilson, J ;

Webster, KE ;

Scott, HS ;

Boyd, RL ;

Peltonen, L ;

Goodnow, CC .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (08) :1015-1026

[78] Aire regulates negative selection of organ-specific T cells [J].

Liston, A ;

Lesage, S ;

Wilson, J ;

Peltonen, L ;

Goodnow, CC .

NATURE IMMUNOLOGY, 2003, 4 (04) :350-354

[79] Crystal structure and nuclear magnetic resonance analyses of the SAND domain from glucocorticoid modulatory element binding protein-1 reveals deoxyribonucleic acid and zinc binding regions [J].

Lo Surdo, P ;

Bottomley, MJ ;

Sattler, M ;

Scheffzek, K .

MOLECULAR ENDOCRINOLOGY, 2003, 17 (07) :1283-1295

[80] A decade of AIRE [J].

Mathis, Diane ;

Benoist, Christophe .

NATURE REVIEWS IMMUNOLOGY, 2007, 7 (08) :645-650

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