Scaffold protein JLP mediates TCR-initiated CD4+T cell activation and CD154 expression.
Scaffold protein JLP mediates TCR-initiated CD4+T cell activation and CD154 expression.
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支架蛋白 JLP 介导 TCR 启动的 CD4 T 细胞活化和 CD154 表达。
DOI：
10.1016/j.molimm.2017.05.006
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Wang Huiming
中科院分区：
文献类型：
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作者：
Yan Qi;Yang Cheng;Fu Qiang;Chen Zhaowei;Liu Shan;Fu Dou;Rahman Rahmat N;Nakazato Ryota;Yoshioka Katsuji;Kung Sam K P;Ding Guohua;Wang Huiming
CD4+T细胞的活化及其诱导的CD154(CD40配体，CD40L)的表达在形成体液免疫和细胞免疫反应中起着关键作用。支架蛋白JLP调节细胞内的信号转导途径和分子运输，是维持细胞功能的重要组成部分，但其在调节CD4+T细胞活化和CD154表达中的作用尚不清楚。在这里，我们展示了JLP在小鼠的淋巴结、胸腺、脾组织以及CD4+T细胞中的表达。使用来自JLP缺陷和JLP野生型小鼠的CD4+T细胞，我们证明JLP缺乏会损害T细胞的增殖、IL-2的产生和TCR刺激下CD154的诱导，但对CD25、CD69和TCR等其他表面分子的表达没有影响。这些观察到的JLP-/-CD_4+T细胞功能受损与核因子-AT激活缺陷和钙离子内流有关，而与丝裂原活化蛋白、核因子-κB和AP-1信号通路无关。我们的研究结果首次表明，JLP在调节CD4+T细胞对TCR刺激的反应中起关键作用，部分是通过介导TCR启动的钙/核因子-AT的激活。
CD4+T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions.Its role in regulating CD4+T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4+T cells. Using CD4+ T cells from jlp-deficient and jlp-wild-type mice, we demonstrated that JLP-deficiency impaired T-cell proliferation, IL-2 production, and CD154 induction upon TCR stimulations, but had no impacts on the expression of other surface molecules such as CD25, CD69, and TCR. These observed impaired T-cell functions in the jlp-/- CD4+T cells were associated with defective NF-AT activation and Ca2+influx, but not the MAPK, NF-κB, as well as AP-1 signaling pathways. Our findings indicated that, for the first time, JLP plays a critical role in regulating CD4+T cells response to TCR stimulation partly by mediating the activation of TCR-initiated Ca2+/NF-AT.