PMID- 37864795
OWN - NLM
STAT- MEDLINE
DCOM- 20231108
LR  - 20231113
IS  - 2211-1247 (Electronic)
VI  - 42
IP  - 10
DP  - 2023 Oct 31
TI  - CD226 maintains regulatory T cell phenotype stability and metabolism by the 
      mTOR/Myc pathway under inflammatory conditions.
PG  - 113306
LID - S2211-1247(23)01318-9 [pii]
LID - 10.1016/j.celrep.2023.113306 [doi]
AB  - Regulatory T (Treg) cells exhibit immunosuppressive phenotypes and particular 
      metabolic patterns with certain degrees of plasticity. Previous studies of the 
      effects of the co-stimulatory molecule CD226 on Treg cells are controversial. 
      Here, we show that CD226 primarily maintains the Treg cell stability and 
      metabolism phenotype under inflammatory conditions. Conditional deletion of CD226 
      within Foxp3(+) cells exacerbates symptoms in murine graft versus host disease 
      models. Treg cell-specific deletion of CD226 increases the Treg cell percentage 
      in immune organs but weakens their immunosuppressive function with a T helper 
      1-like phenotype conversion under inflammation. CD226-deficient Treg cells 
      exhibit reduced oxidative phosphorylation and increased glycolysis rates, which 
      are regulated by the adenosine 5'-monophosphate-activated protein kinase 
      (AMPK)/mammalian target of rapamycin (mTOR)/myelocytomatosis oncogene (Myc) 
      pathway, and inhibition of Myc signaling restores the impaired functions of 
      CD226-deficient Treg cells in an inflammatory disease model of colitis. This 
      study reveals an Myc-mediated CD226 regulation of Treg cell phenotypic stability 
      and metabolism, providing potential therapeutic strategies for targeted 
      interventions of Treg cell-specific CD226 in inflammatory diseases.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Ma, Jingchang
AU  - Ma J
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Hu, Wei
AU  - Hu W
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China; Department of Emergency, The Fifth Medical 
      Center of Chinese PLA General Hospital, #100 Western 4th Ring Road, Beijing 
      100039, China.
FAU - Liu, Yitian
AU  - Liu Y
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Duan, Chujun
AU  - Duan C
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China; Institute of Medical Research, Northwestern 
      Polytechnical University, #127 West Youyi Road, Xi'an, Shaanxi 710072, China.
FAU - Zhang, Dongliang
AU  - Zhang D
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Wang, Yuling
AU  - Wang Y
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Cheng, Kun
AU  - Cheng K
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Yang, Lu
AU  - Yang L
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Wu, Shuwen
AU  - Wu S
AD  - Institute of Medical Research, Northwestern Polytechnical University, #127 West 
      Youyi Road, Xi'an, Shaanxi 710072, China.
FAU - Jin, Boquan
AU  - Jin B
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Zhang, Yuan
AU  - Zhang Y
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China; Institute of Medical Research, Northwestern 
      Polytechnical University, #127 West Youyi Road, Xi'an, Shaanxi 710072, China. 
      Electronic address: zhangyuan_nwpu@nwpu.edu.cn.
FAU - Zhuang, Ran
AU  - Zhuang R
AD  - Department of Immunology, Fourth Military Medical University, #169 West Changle 
      Road, Xi'an, Shaanxi 710032, China; Institute of Medical Research, Northwestern 
      Polytechnical University, #127 West Youyi Road, Xi'an, Shaanxi 710072, China. 
      Electronic address: fmmuzhr@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (CD226 antigen)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Forkhead Transcription Factors/metabolism
MH  - Mammals/metabolism
MH  - Phenotype
MH  - *Proto-Oncogene Proteins c-myc/genetics/metabolism
MH  - Signal Transduction
MH  - *T-Lymphocytes, Regulatory
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - CD226
OT  - CP: Immunology
OT  - Treg cells
OT  - inflammatory diseases
OT  - metabolism
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2023/10/21 19:43
MHDA- 2023/11/06 06:41
CRDT- 2023/10/21 12:36
PHST- 2023/02/27 00:00 [received]
PHST- 2023/09/22 00:00 [revised]
PHST- 2023/10/04 00:00 [accepted]
PHST- 2023/11/06 06:41 [medline]
PHST- 2023/10/21 19:43 [pubmed]
PHST- 2023/10/21 12:36 [entrez]
AID - S2211-1247(23)01318-9 [pii]
AID - 10.1016/j.celrep.2023.113306 [doi]
PST - ppublish
SO  - Cell Rep. 2023 Oct 31;42(10):113306. doi: 10.1016/j.celrep.2023.113306.