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Mechanical force receptor Piezo1 regulates TH9 cell differentiation
Qiuli Yang1, Yejin Cao1, Likun Wang2
1Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Cell Reports
|February 11, 2025
Summary
The mechanical force receptor Piezo1 is crucial for TH9 cell differentiation, a key part of antitumor immunity. Its deficiency impairs this process, impacting tumor development and offering new immunotherapy targets.
Area of Science:
- Immunology
- Cell Biology
- Mechanobiology
Background:
- Interleukin (IL)-9-producing CD4+ T cells (TH9) are vital for antitumor immunity.
- The precise mechanisms governing TH9 cell differentiation are not fully understood.
Purpose of the Study:
- To investigate the role of the mechanical force receptor Piezo1 in TH9 cell differentiation.
- To elucidate the underlying molecular pathways involved in Piezo1-mediated TH9 regulation.
Main Methods:
- Utilized genetic manipulation to assess Piezo1's impact on CD4+ T cells.
- Analyzed the involvement of SIRT3, succinate dehydrogenase A (SDHA), oxidative phosphorylation (OXPHOS), and HIF1α signaling pathways.
- Evaluated the effect of Piezo1 deficiency on TH9 cell differentiation and tumor development in vivo.
Main Results:
- Piezo1 deficiency intrinsically inhibited TH9 cell differentiation, while its ectopic expression promoted it.
- Piezo1 deficiency impaired TH9 cell differentiation, contributing to tumor progression.
- The mechanism involves Piezo1 regulating the SIRT3-SDHA-OXPHOS pathway and activating HIF1α signaling.
Conclusions:
- Piezo1 is a critical regulator of TH9 cell differentiation through a redox metabolism signaling pathway.
- This pathway involves mitochondrial SIRT3-SDHA-dependent OXPHOS and HIF1α signaling.
- Targeting Piezo1-mediated signaling offers potential for novel immunotherapy strategies against cancer.
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