Fluid shear stress enhances T cell activation through Piezo1

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Biology, Vol 20, Iss 1, Pp 1-13 (2022)
Druh dokumentu: article
ISSN: 1741-7007
DOI: 10.1186/s12915-022-01266-7
Popis: 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.
Databáze: Directory of Open Access Journals
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