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
收藏
页码：948 / 957
页数：10
相关论文
共 137 条
[1]   An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains [J].
Aaltonen, J ;
Bjorses, P ;
Perheentupa, J ;
HorelliKuitunen, N ;
Palotie, A ;
Peltonen, L ;
Lee, YS ;
Francis, F ;
Hennig, S ;
Thiel, C ;
Lehrach, H ;
Yaspo, ML .
NATURE GENETICS, 1997, 17 (04) :399-403
[2]   Dependence of self-tolerance on TRAF6-directed development of thymic stroma [J].
Akiyama, T ;
Maeda, S ;
Yamane, S ;
Ogino, K ;
Kasai, M ;
Kajiura, F ;
Matsumoto, M ;
Inoue, J .
SCIENCE, 2005, 308 (5719) :248-251
[3]   The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance [J].
Akiyama, Taishin ;
Shimo, Yusuke ;
Yanai, Hiromi ;
Qin, Junwen ;
Ohshima, Daisuke ;
Maruyama, Yuya ;
Asaumi, Yukiko ;
Kitazawa, Juli ;
Takayanagi, Hiroshi ;
Penninger, Josef M. ;
Matsumoto, Mitsuru ;
Nitta, Takeshi ;
Takahama, Yousuke ;
Inoue, Jun-ichiro .
IMMUNITY, 2008, 29 (03) :423-437
[4]   Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner [J].
Akiyoshi, H ;
Hatakeyama, S ;
Pitkänen, J ;
Mouri, Y ;
Doucas, V ;
Kudoh, J ;
Tsurugaya, K ;
Uchida, D ;
Matsushima, A ;
Oshikawa, K ;
Nakayama, KI ;
Shimizu, N ;
Peterson, P ;
Matsumoto, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (32) :33984-33991
[5]   Autoimmune polyendocrine syndrome type 1 and NALP5, parathyroid autoantigen [J].
Alimohammadi, Mohammad ;
Bjorklund, Peyman ;
Hallgren, Asa ;
Pontynen, Nora ;
Szinnai, Gabor ;
Shikama, Noriko ;
Keller, Marcel P. ;
Ekwall, Olov ;
Kinkel, Sarah A. ;
Husebye, Eystein S. ;
Gustafsson, Jan ;
Rorsman, Fredrik ;
Peltonen, Leena ;
Betterle, Corrado ;
Perheentupa, Jaakko ;
Akerstrom, Goran ;
Westin, Gunnar ;
Scott, Hamish S. ;
Hollaender, Georg A. ;
Kampe, Olle .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (10) :1018-1028
[6]   Generating intrathymic microenvironments to establish T-cell tolerance [J].
Anderson, Graham ;
Lane, Peter J. L. ;
Jenkinson, Eric J. .
NATURE REVIEWS IMMUNOLOGY, 2007, 7 (12) :954-963
[7]   The cellular mechanism of Aire control of T cell tolerance [J].
Anderson, MS ;
Venanzi, ES ;
Chen, ZB ;
Berzins, SP ;
Benoist, C ;
Mathis, D .
IMMUNITY, 2005, 23 (02) :227-239
[8]   Projection of an immunological self shadow within the thymus by the aire protein [J].
Anderson, MS ;
Venanzi, ES ;
Klein, L ;
Chen, ZB ;
Berzins, SP ;
Turley, SJ ;
von Boehmer, H ;
Bronson, R ;
Dierich, A ;
Benoist, C ;
Mathis, D .
SCIENCE, 2002, 298 (5597) :1395-1401
[9]   Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells [J].
Aschenbrenner, Katharina ;
D'Cruz, Louise M. ;
Vollmann, Elisabeth H. ;
Hinterberger, Maria ;
Emmerich, Jan ;
Swee, Lee Kim ;
Rolink, Antonius ;
Klein, Ludger .
NATURE IMMUNOLOGY, 2007, 8 (04) :351-358
[10]   Noise in protein expression scales with natural protein abundance [J].
Bar-Even, Arren ;
Paulsson, Johan ;
Maheshri, Narendra ;
Carmi, Miri ;
O'Shea, Erin ;
Pilpel, Yitzhak ;
Barkai, Naama .
NATURE GENETICS, 2006, 38 (06) :636-643
12345678910