Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation
Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation
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DOI：
10.4049/jimmunol.1701118
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发表时间：
2018-02-15
影响因子：
4.4
通讯作者：
Ganguly, Dipyaman
中科院分区：
文献类型：
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作者：
Liu, Chinky Shiu Chen;Raychaudhuri, Deblina;Ganguly, Dipyaman
tcr识别MHC分子上的肽并诱导下游信号传导，导致激活和克隆扩增。除了TCR与MHC分子上肽的相互作用强度外，机械力有助于最佳的T细胞激活，这反映在固定TCR交联抗体在TCR触发中的效率优于可溶性抗体，尽管没有确定专用的机械转导模块。我们发现专业机械传感器蛋白Piezo1在人类T细胞活化中起关键作用。虽然Piezo1的缺乏会减弱体外TCR触发的下游事件，但Piezo1激动剂可以消除固定TCR交联抗体的需要。Piezo1驱动的ca2 +内流，导致钙蛋白酶激活和皮质肌动蛋白支架的组织，将这种机械传感器与最佳的TCR信号联系起来。因此，我们发现了迄今为止未知的人类T细胞活化的调节机制，并为我们所知的Piezo1机械传感器参与免疫调节提供了第一个证据。
TCRs recognize peptides on MHC molecules and induce downstream signaling, leading to activation and clonal expansion. In addition to the strength of the interaction of TCRs with peptides on MHC molecules, mechanical forces contribute to optimal T cell activation, as reflected by the superior efficiency of immobilized TCR-crosslinking Abs compared with soluble Abs in TCR triggering, although a dedicated mechanotransduction module is not identified. We found that the professional mechanosensor protein Piezo1 is critically involved in human T cell activation. Although a deficiency in Piezo1 attenuates downstream events on ex vivo TCR triggering, a Piezo1 agonist can obviate the need to immobilize TCR-cross-linking Abs. Piezo1-driven Ca 2+ influx, leading to calpain activation and organization of cortical actin scaffold, links this mechanosensor to optimal TCR signaling. Thus, we discovered a hitherto unknown regulatory mechanism for human T cell activation and provide the first evidence, to our knowledge, for the involvement of Piezo1 mechanosensors in immune regulation.