Dendritic cell Piezo1 directs the differentiation of T_H1 and T_reg cells in cancer.

ABSTRACT: Dendritic cells (DCs) play an important role in anti-tumor immunity by inducing T cell differentiation. Herein, we found that the DC mechanical sensor Piezo1 stimulated by mechanical stiffness or inflammatory signals directs the reciprocal differentiation of T_H1 and regulatory T (T_reg) cells in cancer. Genetic deletion of Piezo1 in DCs inhibited the generation of T_H1 cells while driving the development of T_reg cells in promoting cancer growth in mice. Mechanistically, Piezo1-deficient DCs regulated the secretion of the polarizing cytokines TGFβ1 and IL-12, leading to increased TGFβR2-p-Smad3 activity and decreased IL-12Rβ2-p-STAT4 activity while inducing the reciprocal differentiation of T_reg and T_H1 cells. In addition, Piez

SUBMITTER: Wang Y 

PROVIDER: S-EPMC9451538 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature