Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms.
Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms.
复制标题
DOI：
--
复制
发表时间：
2006
期刊：
影响因子：
32.4
通讯作者：
Ming O. Li;Shomyseh Sanjabi;R. Flavell
中科院分区：
文献类型：
--
作者：
Ming O. Li;Shomyseh Sanjabi;R. Flavell
转化生长因子- β (tgf - β)在抑制T细胞功能中的作用已通过显性阴性tgf - β受体转基因模型进行了研究；然而，tgf - β信号对T细胞的全面影响以及tgf - β信号的机制仍然知之甚少。本研究表明，T细胞特异性缺失tgf - β受体II的小鼠发生与T细胞激活和分化相关的致死性炎症。此外，tgf - β信号积极调节T细胞的发育和稳态。CD8+ T细胞和NKT细胞的发育、外周foxp3表达调节性T细胞的维持以及CD4+ T细胞的存活都依赖于tgf - β信号。T辅助细胞1 （Th1）的分化和活化CD4+ T细胞的存活都需要T-bet， T-bet是tgf - β调节的转录因子，它控制Th1细胞中CD122的表达和IL-15信号传导。这项研究揭示了T细胞中tgf - β信号的多效性，这可能确保体内T细胞库的多样性和自我耐受性。
The role of transforming growth factor-beta (TGF-beta) in inhibiting T cell functions has been studied with dominant-negative TGF-beta receptor transgenic models; however, the full impact of TGF-beta signaling on T cells and the mechanisms by which TGF-beta signals remain poorly understood. Here we show that mice with T cell-specific deletion of TGF-beta receptor II developed lethal inflammation associated with T cell activation and differentiation. In addition, TGF-beta signaling positively regulated T cell development and homeostasis. Development of CD8+ T cells and NKT cells, maintenance of peripheral Foxp3-expressing regulatory T cells, and survival of CD4+ T cells all depended on TGF-beta signaling. Both T helper 1 (Th1) differentiation and survival of activated CD4+ T cells required T-bet, the TGF-beta-regulated transcription factor, which controlled CD122 expression and IL-15 signaling in Th1 cells. This study reveals pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo.