Fluid shear stress enhances T cell activation through Piezo1.
Fluid shear stress enhances T cell activation through Piezo1.
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DOI：
10.1186/s12915-022-01266-7
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发表时间：
2022-03-09
期刊：
影响因子：
5.4
通讯作者：
King MR
中科院分区：
文献类型：
--
作者：
Hope JM;Dombroski JA;Pereles RS;Lopez-Cavestany M;Greenlee JD;Schwager SC;Reinhart-King CA;King MR
T细胞的激活既是一个生化过程，也是一个机械过程。在这项研究中，我们使用锥板粘度计系统处理Jurkat和原代人类T细胞，以流体切应力(FSS)通过机械手段增强T细胞的激活。FSS联合可溶性和微球结合的CD3/CD2 8抗体可增加T细胞活化所必需的信号蛋白的激活能力，如Zap70、活化T细胞的核因子、核因子-κB和AP-1(激活蛋白1)。FSS治疗还增强了T细胞持续激活和功能所必需的细胞因子肿瘤坏死因子-α、白介素2和干扰素-γ的表达。FSS对T细胞的激活作用呈钙依赖性。钙信号受机械敏感离子通道Piezo1控制，GsMTx-4和Piezo1基因敲除降低了FSS对ZAP70的磷酸化。这些结果显示了一种有趣的T细胞激活的新动态，因为循环系统由不同程度的FSS组成，可能在T细胞功能中起到促炎作用。由于高血压是一种以异常血流为特征的疾病，并与多种自身免疫性疾病相关，因此该结果还确定了T细胞激活与FSS之间潜在的病理生理关系。网上版载有补充材料，可在10.1186/s12915-022-01266-7查阅。
T cell activation is a mechanical process as much as it is a biochemical process. In this study, we used a cone-and-plate viscometer system to treat Jurkat and primary human T cells with fluid shear stress (FSS) to enhance the activation of the T cells through mechanical means. The FSS treatment of T cells in combination with soluble and bead-bound CD3/CD28 antibodies increased the activation of signaling proteins essential for T cell activation, such as zeta-chain-associated protein kinase-70 (ZAP70), nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), and AP-1 (activator protein 1). The FSS treatment also enhanced the expression of the cytokines tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), and interferon gamma (IFN-γ), which are necessary for sustained T cell activation and function. The enhanced activation of T cells by FSS was calcium dependent. The calcium signaling was controlled by the mechanosensitive ion channel Piezo1, as GsMTx-4 and Piezo1 knockout reduced ZAP70 phosphorylation by FSS. These results demonstrate an intriguing new dynamic to T cell activation, as the circulatory system consists of different magnitudes of FSS and could have a proinflammatory role in T cell function. The results also identify a potential pathophysiological relationship between T cell activation and FSS, as hypertension is a disease characterized by abnormal blood flow and is correlated with multiple autoimmune diseases. The online version contains supplementary material available at 10.1186/s12915-022-01266-7.
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