BMC Biology (Mar 2022)

Fluid shear stress enhances T cell activation through Piezo1

  • Jacob M. Hope,
  • Jenna A. Dombroski,
  • Rebecca S. Pereles,
  • Maria Lopez-Cavestany,
  • Joshua D. Greenlee,
  • Samantha C. Schwager,
  • Cynthia A. Reinhart-King,
  • Michael R. King

DOI
https://doi.org/10.1186/s12915-022-01266-7
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 13

Abstract

Read online

Abstract 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-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. 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.

Keywords