Dependence of self-tolerance on TRAF6-directed development of thymic stroma
Dependence of self-tolerance on TRAF6-directed development of thymic stroma
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DOI：
10.1126/science.1105677
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发表时间：
2005-04-08
期刊：
影响因子：
56.9
通讯作者：
Inoue, J
中科院分区：
文献类型：
--
作者：
Akiyama, T;Maeda, S;Inoue, J
胸腺的微环境由胸腺上皮细胞（TEC）产生，并且对于诱导免疫自我耐受或发育T细胞是必不可少的。然而，TEC分化和胸腺区室化的分子机制尚未完全了解。在这里，我们表明，在肿瘤坏死因子受体相关因子（TRAF）6的缺陷，结果在髓TECs（mTECs）的无序分布和成熟的mTECs的情况下。TRAF 6（-/-）胚胎胸腺基质植入无胸腺裸鼠体内可诱导自身免疫。因此，TRAF 6指导胸腺基质的发育，并代表了自身耐受和自身免疫调节的关键点。
The microenvironments of the thymus are generated by thymic epithelial cells (TECs) and are essential for inducing immune self-toterance 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.