Rasal3-mediated T cell survival is essential for inflammatory responses
Rasal3-mediated T cell survival is essential for inflammatory responses
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DOI：
10.1016/j.bbrc.2017.12.159
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发表时间：
2018-01-29
影响因子：
3.1
通讯作者：
Suzuki, Harumi
中科院分区：
文献类型：
--
作者：
Muro, Ryunosuke;Nitta, Takeshi;Suzuki, Harumi
Rasimitogen活化蛋白激酶（MAPK）通路的精细调节在控制各种类型细胞的存活、增殖和发育中至关重要。Ras活化蛋白样3（Rasal 3）是T细胞特异性Ras GTP酶活化蛋白，负性调节T细胞受体（TCR）诱导的Ras/MAPK通路的活化。Rasal 3缺陷型小鼠表现出幼稚T细胞数量的减少，因为幼稚T细胞的存活需要Rasal 3。在目前的研究中，我们观察到Rasal 3缺陷小鼠的T辅助细胞（Th 1）和T辅助细胞（Th 2）依赖性接触性超敏反应得到改善，沿着局部淋巴结T细胞明显短缺。活化的Rasa 13缺陷型T细胞表现出增加的细胞死亡和减少的Bcl 2表达，表明Rasa 13不仅是幼稚T细胞而且是活化T细胞存活所需的。总的来说，Rasal 3通过体内初始T细胞和活化T细胞的存活来控制炎症反应的程度。(C)2017爱思唯尔公司All rights reserved.
Fine regulation of the Rasimitogen-activating protein kinase (MAPK) pathway is crucial in controlling the survival, proliferation, and development of various types of cells. Ras-activating protein-like 3 (Rasal3) is a T cell-specific Ras GTPase-activating protein that negatively regulates T cell receptor (TCR)-induced activation of Ras/MAPK pathway. Rasal3-deficient mice showed a decreased number of naive T cells because Rasal3 is required for the survival of naive T cells. In the current study, we observed ameliorated Typel T helper (Th1) cell- and Type2 T helper (Th2) cell-dependent contact hypersensitivity reactions in Rasal3-deficient mice, along with a marked shortage of T cells at regional lymph node. Activated Rasa13-deficient T cells showed an increased cell death with reduced Bc12 expression, suggesting that Rasal3 is required for the survival of not only naive T cells but also activated T cells. Collectively, Rasal3 controls the magnitude of inflammatory responses through the survival of both naive T cells and activated T cells in vivo. (C) 2017 Elsevier Inc. All rights reserved.