PMID- 35993548
OWN - NLM
STAT- MEDLINE
DCOM- 20220909
LR  - 20220919
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 11
DP  - 2022 Aug 22
TI  - Dendritic cell Piezo1 directs the differentiation of T(H)1 and T(reg) cells in 
      cancer.
LID - 10.7554/eLife.79957 [doi]
LID - e79957
AB  - 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(H)1 and regulatory T (T(reg)) cells in cancer. Genetic 
      deletion of Piezo1 in DCs inhibited the generation of T(H)1 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 TGFbeta1 and IL-12, leading to increased TGFbetaR2-p-Smad3 activity and 
      decreased IL-12Rbeta2-p-STAT4 activity while inducing the reciprocal differentiation 
      of T(reg) and T(H)1 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 T(H)1 and 
      T(reg) 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.
CI  - (c) 2022, Wang, Yang, Jia et al.
FAU - Wang, Yuexin
AU  - Wang Y
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Yang, Hui
AU  - Yang H
AD  - Department of Immunology, School of Basic Medical Sciences, Fudan University, 
      Shanghai, China.
FAU - Jia, Anna
AU  - Jia A
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Wang, Yufei
AU  - Wang Y
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Yang, Qiuli
AU  - Yang Q
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Dong, Yingjie
AU  - Dong Y
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Hou, Yueru
AU  - Hou Y
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Cao, Yejin
AU  - Cao Y
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Dong, Lin
AU  - Dong L
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
FAU - Bi, Yujing
AU  - Bi Y
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
FAU - Liu, Guangwei
AU  - Liu G
AUID- ORCID: 0000-0002-6008-2891
AD  - Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of 
      Education, College of Life Sciences, Beijing Normal University, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20220822
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Ion Channels)
RN  - 0 (Piezo1 protein, mouse)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Dendritic Cells
MH  - Interleukin-12/metabolism
MH  - Ion Channels/*metabolism
MH  - Mice
MH  - *Neoplasms/pathology
MH  - T-Lymphocytes, Regulatory
MH  - *Th1 Cells
MH  - Th17 Cells/metabolism
MH  - Th2 Cells
MH  - Tumor Microenvironment
PMC - PMC9451538
OTO - NOTNLM
OT  - Piezo1
OT  - T cell differentiation
OT  - cancer
OT  - cancer biology
OT  - dendritic cell
OT  - immunology
OT  - inflammation
OT  - mouse
OT  - tumor microenvironment
COIS- YW, HY, AJ, YW, QY, YD, YH, YC, LD, YB, GL No competing interests declared
EDAT- 2022/08/23 06:00
MHDA- 2022/09/11 06:00
PMCR- 2022/08/22
CRDT- 2022/08/22 07:54
PHST- 2022/05/03 00:00 [received]
PHST- 2022/08/20 00:00 [accepted]
PHST- 2022/08/23 06:00 [pubmed]
PHST- 2022/09/11 06:00 [medline]
PHST- 2022/08/22 07:54 [entrez]
PHST- 2022/08/22 00:00 [pmc-release]
AID - 79957 [pii]
AID - 10.7554/eLife.79957 [doi]
PST - epublish
SO  - Elife. 2022 Aug 22;11:e79957. doi: 10.7554/eLife.79957.