Death in the AIRE

被引：13

作者：

Ferguson, Brian J. ^{[2
,3
]}

Cooke, Anne ^{[2
,3
]}

Peterson, Paert ^{[4
]}

Rich, Tina ^{[1
]}

机构：

[1] Univ Glasgow, Inst Comparat Med, Glasgow G61 1QH, Lanark, Scotland

[2] Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England

[3] Univ Cambridge, Dept Pathol, Div Cellular Pathol, Cambridge CB2 1QP, England

[4] Univ Tartu, EE-50411 Biomedicum, Estonia

来源：

TRENDS IN IMMUNOLOGY | 2008年 / 29卷 / 07期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1016/j.it.2008.03.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

When thymic epithelia begin to synthesize peripheral tissue antigens such as insulin, we are seeing the result of autoimmune regulator (AIRE) activity and the workings of central tolerance. AIRE is an extraordinary protein that repatterns the transcriptome of medullary thymic epithelia (mTECs) to produce a stroma decorated with peripheral self-peptides. These peptidic arrays are used to purge self-reactive T cells, thereby averting autoimmunity. We now propose that an inherently cytotoxic event such as global chromatin modification paves the way for AIRE action. This injury stimulus might impose temporal restrictions for the T-cell education process and is endured, at least transiently, by the unique cellular environment provided by the medullary thymic epithelia.

引用

收藏

页码：306 / 312

页数：7

相关论文

共 63 条

[11] AIRE's CARD revealed, a new structure for central tolerance provokes transcriptional plasticity [J].

Ferguson, Brian J. ;

Alexander, Clare ;

Rossi, Simona W. ;

Liiv, Ingrid ;

Rebane, Ana ;

Worth, Catherine L. ;

Wong, Joyce ;

Laan, Martti ;

Peterson, Paert ;

Jenkinson, Eric J. ;

Anderson, Graham ;

Scott, Hamish S. ;

Cooke, Anne ;

Rich, Tina .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (03) :1723-1731

[12] Nuclear organization of the genome and the potential for gene regulation [J].

Fraser, Peter ;

Bickmore, Wendy .

NATURE, 2007, 447 (7143) :413-417

[13] Late activation of stress kinases (SAPK/JNK) by genotoxins requires the DNA repair proteins DNA-PKCS and CSB [J].

Fritz, G ;

Kaina, B .

MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (02) :851-861

[14] Poly(ADP-ribose) polymerase and Ku autoantigen form a complex and synergistically bind to matrix attachment sequences [J].

Galande, S ;

Kohwi-Shigematso, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (29) :20521-20528

[15] Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation [J].

Gallegos, AM ;

Bevan, MJ .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (08) :1039-1049

[16] COHABITATION OF SCAFFOLD BINDING REGIONS WITH UPSTREAM ENHANCER ELEMENTS OF 3 DEVELOPMENTALLY REGULATED GENES OF DROSOPHILA-MELANOGASTER [J].

GASSER, SM ;

LAEMMLI, UK .

CELL, 1986, 46 (04) :521-530

[17] Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity [J].

Gavanescu, Irina ;

Kessler, Benedikt ;

Ploegh, Hidde ;

Benoist, Christophe ;

Mathis, Diane .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (11) :4583-4587

[18] Aire-dependent alterations in medullary thymic epithelium indicate a role for Aire in thymic epithelial differentiation [J].

Gillard, Geoffrey O. ;

Dooley, James ;

Erickson, Matthew ;

Peltonen, Leena ;

Farr, Andrew G. .

JOURNAL OF IMMUNOLOGY, 2007, 178 (05) :3007-3015

[19] An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus [J].

Giraud, Matthieu ;

Taubert, Richard ;

Vandiedonck, Claire ;

Ke, Xiayi ;

Levi-Strauss, Matthieu ;

Pagani, Franco ;

Baralle, Francisco E. ;

Eymard, Bruno ;

Tranchant, Christine ;

Gajdos, Philippe ;

Vincent, Angela ;

Willcox, Nick ;

Beeson, David ;

Kyewski, Bruno ;

Garchon, Henri-Jean .

NATURE, 2007, 448 (7156) :934-U9

[20] Regulating self-tolerance by deregulating gene expression [J].

Gotter, J ;

Kyewski, B .

CURRENT OPINION IN IMMUNOLOGY, 2004, 16 (06) :741-745

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