PMID- 33203937
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20240403
IS  - 2042-0226 (Electronic)
IS  - 1672-7681 (Print)
IS  - 1672-7681 (Linking)
VI  - 18
IP  - 9
DP  - 2021 Sep
TI  - TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis 
      in effector and memory CD8 T cells.
PG  - 2262-2274
LID - 10.1038/s41423-020-00583-7 [doi]
AB  - Generation and maintenance of antigen-specific effector and memory T cells are 
      central events in immune responses against infections. We show that TNF 
      receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in 
      effector and memory CD8 T cells required for immune responses against infections. 
      This signaling axis involves activation of Tpl2 and its downstream kinase ERK by 
      NF-kappaB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK 
      mediates Tpl2 activation by stimulating the phosphorylation and degradation of 
      the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK 
      signaling under normal conditions, uncontrolled NIK activation due to loss of its 
      negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, 
      leading to severe defects in ERK activation and effector/memory CD8 T cell 
      survival. Thus, TRAF2 controls a previously unappreciated signaling axis 
      mediating effector/memory CD8 T cell survival and protective immunity.
CI  - (c) 2020. CSI and USTC.
FAU - Xie, Xiaoping
AU  - Xie X
AUID- ORCID: 0000-0001-6616-1059
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Zhu, Lele
AU  - Zhu L
AUID- ORCID: 0000-0002-1732-8753
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Jie, Zuliang
AU  - Jie Z
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Li, Yanchuan
AU  - Li Y
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Gu, Meidi
AU  - Gu M
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Zhou, Xiaofei
AU  - Zhou X
AUID- ORCID: 0000-0002-9289-2215
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
AD  - Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic 
      Biology and Immunology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 
      221004, Jiangsu, China.
FAU - Chang, Jae-Hoon
AU  - Chang JH
AUID- ORCID: 0000-0002-1001-6570
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Republic of Korea.
FAU - Ko, Chun-Jung
AU  - Ko CJ
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Cheng, Xuhong
AU  - Cheng X
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA.
FAU - Sun, Shao-Cong
AU  - Sun SC
AUID- ORCID: 0000-0001-7353-9400
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 
      Fannin Street, Box 902, Houston, TX, 77030, USA. ssun@mdanderson.org.
AD  - MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, 
      Houston, TX, 77030, USA. ssun@mdanderson.org.
LA  - eng
GR  - R01 AI064639/AI/NIAID NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R01 GM084459/GM/NIGMS NIH HHS/United States
GR  - R37 AI064639/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20201117
PL  - China
TA  - Cell Mol Immunol
JT  - Cellular & molecular immunology
JID - 101242872
RN  - 0 (NF-kappa B)
RN  - 0 (TNF Receptor-Associated Factor 2)
SB  - IM
MH  - *CD8-Positive T-Lymphocytes/metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - *Signal Transduction
MH  - TNF Receptor-Associated Factor 2/metabolism
PMC - PMC8429472
OTO - NOTNLM
OT  - Bacterial infection
OT  - Effector and memory CD8 T cells
OT  - NIK
OT  - Protective immunity
OT  - T cell survival
OT  - TRAF2
OT  - Tpl2
COIS- The authors declare no competing interests.
EDAT- 2020/11/19 06:00
MHDA- 2022/04/01 06:00
PMCR- 2022/09/01
CRDT- 2020/11/18 05:54
PHST- 2020/06/25 00:00 [received]
PHST- 2020/10/21 00:00 [accepted]
PHST- 2020/11/19 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2020/11/18 05:54 [entrez]
PHST- 2022/09/01 00:00 [pmc-release]
AID - 10.1038/s41423-020-00583-7 [pii]
AID - 583 [pii]
AID - 10.1038/s41423-020-00583-7 [doi]
PST - ppublish
SO  - Cell Mol Immunol. 2021 Sep;18(9):2262-2274. doi: 10.1038/s41423-020-00583-7. Epub 
      2020 Nov 17.