mTORC1 Signaling Controls TLR2-Mediated T-Cell Activation by Inducing TIRAP Expression
mTORC1 Signaling Controls TLR2-Mediated T-Cell Activation by Inducing TIRAP Expression
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DOI：
10.1016/j.celrep.2020.107911
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发表时间：
2020-07-21
期刊：
影响因子：
8.8
通讯作者：
Saito, Takashi
中科院分区：
文献类型：
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作者：
Imanishi, Takayuki;Unno, Midori;Saito, Takashi
效应T细胞而非初始T细胞通过toll样受体-2（TLR 2）刺激活化，导致细胞因子产生和增殖。我们发现，差异反应是由于缺乏衔接蛋白TIRAP在幼稚T细胞中的表达。TIRAP表达在T细胞受体（TCR）刺激后被诱导，并通过强白细胞介素-2（IL-2）信号维持。TIRAP的表达需要TCR和IL-2诱导的mTORC 1活化。TLR 2刺激诱导核因子κ B（NF-κ B）和ERK的活化，导致在高浓度IL-2中培养的辅助性T细胞1（Th 1）产生的干扰素-γ（IFN-γ）比在低浓度IL-2中培养的细胞高得多。相反，TLR 2刺激通过TIRAP诱导mTORC 1活化，这对于TLR 2介导的IFN-γ产生是必需的。这些数据表明，mT 0 RC 1信号通过诱导TIRAP表达赋予对TLR 2信号传导的应答，并且TIRAP-mT 0 RC 1轴对于效应T细胞的TLR 2介导的IFN-γ产生是关键的。
Effector, but not naive, T cells are activated by toll-like receptor-2 (TLR2) stimulation, leading to cytokine production and proliferation. We found that the differential response is attributable to the lack of expression of the adaptor protein TIRAP in naive T cells. TIRAP expression is induced upon T-cell receptor (TCR) stimulation and sustained by strong interleukin-2 (IL-2) signals. Expression of TIRAP requires TCR- and IL-2-induced mTORC1 activation. TLR2 stimulation induced the activation of nuclear factor kappa B (NF-kappa B) and ERK, leading to much higher production of interferon-gamma (IFN-gamma) by T helper 1 (Th1) cells cultured in a high concentration of IL-2 than by those cultured in a low concentration of IL-2. In contrast, TLR2 stimulation induces mTORC1 activation through TIRAP, which is essential for TLR2-mediated IFN-gamma production. These data demonstrate that the mTORC1 signal confers the response to TLR2 signaling by inducing TIRAP expression and that the TIRAP-mTORC1 axis is critical for TLR2-mediated IFN-gamma production by effector T cells.