TRAF6 directs commitment to regulatory T cells in thymocytes
TRAF6 directs commitment to regulatory T cells in thymocytes
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DOI：
10.1111/j.1365-2443.2011.01500.x
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发表时间：
2011-04-01
期刊：
影响因子：
2.1
通讯作者：
Akiyama, Taishin
中科院分区：
文献类型：
--
作者：
Shimo, Yusuke;Yanai, Hiromi;Akiyama, Taishin
调节性T细胞(Tregs)是CD4+辅助T细胞的一个亚群，对免疫自身耐受至关重要。Tregs的发育或功能缺陷会导致人类和小鼠的自身免疫性疾病。虽然已知Treg主要在胸腺发育，但Treg发育的分子机制尚不完全清楚。TRAF6基因缺陷小鼠的胸腺Treg发育存在严重缺陷。体外胎儿胸腺器官培养实验表明，这种缺陷是由于胸腺细胞中缺少TRAF6所致。此外，混合胎肝移植实验显示，由Traf6-/-造血细胞分化而来的Foxp3+细胞在胸腺中的发育受到特异性损害，这表明Treg发育过程中对TRAF6的细胞内在需求。另一方面，TRAF6不是传统的CD4+T细胞发育所必需的。此外，缺乏TRAF6并不影响体外培养的CD4+T细胞中依赖于转化生长因子β的Foxp3的诱导作用。总体而言，我们的数据表明，TRAF6在未成熟胸腺细胞以细胞固有方式向胸腺树突状细胞承诺方面发挥着重要作用。
Regulatory T cells (Tregs), a subset of CD4+ helper T cells, are crucial for immunological self-tolerance. Defect in development or function of Tregs results in autoimmune disease in human and mice. Whereas it is known that Tregs mainly develop in the thymus, the molecular mechanism underlying development of Treg is not fully understood. TRAF6-deficient mice showed a severe defect in the Treg development in thymus. In vitro fetal thymic organ culture experiments indicated that the defect is ascribed to the absence of TRAF6 in thymic cells. Moreover, mixed fetal liver transfer experiments revealed that the development of Foxp3+ cells differentiated from Traf6-/- hematopoietic cells was specifically impaired in the thymus, indicating cell-intrinsic requirement for TRAF6 in the Treg development. On the other hand, TRAF6 is not required for the development of conventional CD4+ T cell. In addition, TGF beta-dependent induction of Foxp3 in CD4+ T cells in vitro was not impaired by the absence of TRAF6. Overall, our data indicate that TRAF6 plays an essential role on the commitment of immature thymocytes to thymic Tregs in cell-intrinsic fashion.