PMID- 35069527
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220228
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - PP2Cdelta Controls the Differentiation and Function of Dendritic Cells Through 
      Regulating the NSD2/mTORC2/ACLY Pathway.
PG  - 751409
LID - 10.3389/fimmu.2021.751409 [doi]
LID - 751409
AB  - Dendritic cells (DCs) are recognized as a key orchestrator of immune response and 
      homeostasis, deregulation of which may lead to autoimmunity such as experimental 
      autoimmune encephalomyelitis (EAE). Herein we show that the phosphatase PP2Cdelta 
      played a pivotal role in regulating DC activation and function, as PP2Cdelta ablation 
      caused aberrant maturation, activation, and Th1/Th17-priming of DCs, and hence 
      induced onset of exacerbated EAE. Mechanistically, PP2Cdelta restrained the 
      expression of the essential subunit of mTORC2, Rictor, primarily through 
      de-phosphorylating and proteasomal degradation of the methyltransferase NSD2 via 
      CRL4(DCAF2) E3 ligase. Loss of PP2Cdelta in DCs accordingly sustained activation of 
      the Rictor/mTORC2 pathway and boosted glycolytic and mitochondrial metabolism. 
      Consequently, ATP-citrate lyse (ACLY) was increasingly activated and catalyzed 
      acetyl-CoA for expression of the genes compatible with hyperactivated DCs under 
      PP2Cdelta deletion. Collectively, our findings demonstrate that PP2Cdelta has an 
      essential role in controlling DCs activation and function, which is critical for 
      prevention of autoimmunity.
CI  - Copyright (c) 2022 Lv, Jin, Liang, Wu, Kang, Su, Dong, Wang, Ma and Shi.
FAU - Lv, Nianyin
AU  - Lv N
AD  - Department of Immunology, Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Jin, Sufeng
AU  - Jin S
AD  - Department of Clinical Laboratory, The Children's Hospital, Zhejiang University 
      School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 
      China.
AD  - Key Lab of Inflammation and Immunoregulation, Hangzhou Normal University School 
      of Medicine, Hangzhou, China.
FAU - Liang, Zihao
AU  - Liang Z
AD  - Department of Immunology, Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Wu, Xiaohui
AU  - Wu X
AD  - Department of Immunology, Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Kang, Yanhua
AU  - Kang Y
AD  - Department of Immunology, Nanjing University of Chinese Medicine, Nanjing, China.
AD  - Key Lab of Inflammation and Immunoregulation, Hangzhou Normal University School 
      of Medicine, Hangzhou, China.
FAU - Su, Lan
AU  - Su L
AD  - Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, China.
FAU - Dong, Yeping
AU  - Dong Y
AD  - Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, China.
FAU - Wang, Bingwei
AU  - Wang B
AD  - College of Medicine and Integrated Medicine, Nanjing University of Chinese 
      Medicine, Nanjing, China.
FAU - Ma, Tonghui
AU  - Ma T
AD  - College of Medicine and Integrated Medicine, Nanjing University of Chinese 
      Medicine, Nanjing, China.
FAU - Shi, Liyun
AU  - Shi L
AD  - Department of Immunology, Nanjing University of Chinese Medicine, Nanjing, China.
AD  - Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220107
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (WHSC1 protein, mouse)
RN  - EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 3.1.3.16 (Ppm1d protein, mouse)
RN  - EC 3.1.3.16 (Protein Phosphatase 2C)
SB  - IM
MH  - ATP Citrate (pro-S)-Lyase/genetics/*immunology
MH  - Animals
MH  - Cell Differentiation/genetics/*immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Histone-Lysine N-Methyltransferase/genetics/*immunology
MH  - Mechanistic Target of Rapamycin Complex 2/genetics/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Protein Phosphatase 2C/genetics/*immunology
MH  - Signal Transduction/genetics/*immunology
PMC - PMC8777276
OTO - NOTNLM
OT  - PP2Cdelta
OT  - autoimmunity
OT  - dendritic cells
OT  - differentiation
OT  - mTORC2
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/25 06:00
MHDA- 2022/03/01 06:00
PMCR- 2021/01/01
CRDT- 2022/01/24 08:49
PHST- 2021/08/01 00:00 [received]
PHST- 2021/12/16 00:00 [accepted]
PHST- 2022/01/24 08:49 [entrez]
PHST- 2022/01/25 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.751409 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jan 7;12:751409. doi: 10.3389/fimmu.2021.751409. eCollection 
      2021.