期刊
BMC BIOLOGY
卷 20, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12915-022-01266-7
关键词
Fluid shear stress; Piezo1; T cells; Mechanotransduction
类别
资金
- National Institutes of Health [R01CA256054]
- National Science Foundation Graduate Research Fellowship
This study enhances the activation of T cells through mechanical means and finds that fluid shear stress treatment can increase the activation of signaling proteins and cytokine expression in T cells. These results reveal a new dynamic to T cell activation and suggest a potential pathophysiological relationship between T cell activation and fluid shear stress.
Background 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. Results 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-kappa B), and AP-1 (activator protein 1). The FSS treatment also enhanced the expression of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), and interferon gamma (IFN-gamma), 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. Conclusions 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.
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