Piezo1 selectively reinforces TGF-β1-induced IgA class switching by inducing the Smad3 phosphorylation 3493

Description Piezo1 is mechanosensitive cationic channel that controls Ca2+ influx, and transcription of several genes and cell migration. According to recent studies, Piezo1 affects regulatory T cells differentiation and provides a critical role in B cell responses to membrane-presented antigens. Nevertheless, the role of Piezo1 in Ab production has not been understood yet. In this study, we examined the role of Piezo1 in Ig class switching and Ab production by mouse B cells using qRT-PCR, flow cytometric analysis, and isotype-specific ELISA. Piezo1 agonist, Yoda1, elevated intracellular Ca2+ and upregulated TGF-β1-induced germline α transcript (GLTα)/post-switch α transcript (PSTα) expression, surface IgA expression, and IgA production selectively. In contrast, Piezo1 inhibitor, OB-1, decreased IgA class switching. Additionally, TGF-β1-induced GLTα/PSTα expression were lowered in Piezo1 knockdown B cells. Furthermore, TGF-β1-induced Smad3 phosphorylation was upregulated by Yoda1. Thus, these results demonstrate that Piezo1 selectively enhances TGF-β1-induced IgA class switching via Smad3 phosphorylation, leading to IgA production in B cells.