Dependence of self-tolerance on TRAF6-directed development of thymic stroma.
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.
Akiyama
Taishin
T
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Maeda
Shiori
S
Yamane
Sayaka
S
Ogino
Kaori
K
Kasai
Michiyuki
M
Kajiura
Fumiko
F
Matsumoto
Mitsuru
M
Inoue
Jun-ichiro
J
D000818:Animals; D015551:Autoimmunity; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins / Q000502:physiology; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology; D048029:TNF Receptor-Associated Factor 6 / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000502:physiology
D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D048029:TNF Receptor-Associated Factor 6; D014157:Transcription Factors; D051841:Transcription Factor RelB