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Science 308 (5719): 248-251

Copyright © 2005 by the American Association for the Advancement of Science

Dependence of Self-Tolerance on TRAF6-Directed Development of Thymic Stroma

Taishin Akiyama,1 Shiori Maeda,1 Sayaka Yamane,1 Kaori Ogino,1 Michiyuki Kasai,2 Fumiko Kajiura,3 Mitsuru Matsumoto,3 Jun-ichiro Inoue1*

Abstract: The microenvironments of the thymus are generated by thymic epithelial cells (TECs) and are essential for inducing immune self-tolerance or developing T cells. However, the molecular mechanisms that underlie the differentiation of TECs and thymic compartmentalization are not fully understood. Here we show that deficiency in the tumor necrosis factor receptor–associated factor (TRAF) 6 results in disorganized distribution of medullary TECs (mTECs) and the absence of mature mTECs. Engraftment of thymic stroma of TRAF6-/- embryos into athymic nude mice induced autoimmunity. Thus, TRAF6 directs the development of thymic stroma and represents a critical point of regulation for self-tolerance and autoimmunity.

1 Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108–8639, Japan.
2 Division of Bacterial and Blood Products, National Institute of Infectious Disease, Gakuen, Musashimurayama-shi, Tokyo 208–0011, Japan.
3 Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Kuramoto, Tokushima 770–8503, Japan.

* To whom correspondence should be addressed. E-mail: jun-i{at}

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