| First Author | Wang Y | Year | 2022 |
| Journal | Elife | Volume | 11 |
| PubMed ID | 35993548 | Mgi Jnum | J:344003 |
| Mgi Id | MGI:7335643 | Doi | 10.7554/eLife.79957 |
| Citation | Wang Y, et al. (2022) Dendritic cell Piezo1 directs the differentiation of TH1 and Treg cells in cancer. Elife 11:e79957 |
| abstractText | 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 TH1 and regulatory T (Treg) cells in cancer. Genetic deletion of Piezo1 in DCs inhibited the generation of TH1 cells while driving the development of Treg cells in promoting cancer growth in mice. Mechanistically, Piezo1-deficient DCs regulated the secretion of the polarizing cytokines TGFbeta1 and IL-12, leading to increased TGFbetaR2-p-Smad3 activity and decreased IL-12Rbeta2-p-STAT4 activity while inducing the reciprocal differentiation of Treg and TH1 cells. In addition, Piezo1 integrated the SIRT1-hypoxia-inducible factor-1 alpha (HIF1alpha)-dependent metabolic pathway and calcium-calcineurin-NFAT signaling pathway to orchestrate reciprocal TH1 and Treg lineage commitment through DC-derived IL-12 and TGFbeta1. Our studies provide critical insight for understanding the role of the DC-based mechanical regulation of immunopathology in directing T cell lineage commitment in tumor microenvironments. |
