PMID- 35128379
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220208
IS  - 2590-1532 (Electronic)
IS  - 2590-1532 (Linking)
VI  - 4
IP  - 1
DP  - 2022 Mar
TI  - TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ 
      MDM2 pathway after acute insult.
PG  - 100062
LID - 10.1016/j.cytox.2022.100062 [doi]
LID - 100062
AB  - Th17 cells induced immunosuppression plays a vital role in sepsis. As a member of 
      the tumor necrosis factor alpha induced protein 8 (TNFAIP8) family, TNFAIP8 is 
      associated with different physiopathological conditions with immunological 
      responses. However, its potential roles in regulating Th17 cells after the acute 
      insult have not been fully elucidated. In this study, sepsis was induced by cecal 
      ligation and puncture (CLP) in the male adult C57BL/6 mice. The stable TNFAIP8 
      knockdown (KD) Th17 cells were established by infecting with lentivirus carrying 
      TNFAIP8-specific shRNA. CCK-8 assay was conducted to evaluate Th17 cell 
      proliferation, and Annexin V/7-AAD assay was applied for apoptosis measurement by 
      flow cytometry. The alterations of p53/ p21/ MDM2 pathway were assessed by 
      Western blot. We observed that a high TNFAIP8 expression level was related to 
      acute injury in septic mice. TNFAIP8 silencing suppressed Th17 cell proliferation 
      and cytokine production in vivo and in vitro. In addition, TNFAIP8 KD increased 
      Th17 cell apoptosis in septic mice. Furthermore, TNFAIP8 seems to affect the 
      immune function of Th17 cells by regulating p53/ p21/ MDM2 signaling processes. 
      We found that TNFAIP8 KD caused the up-regulation of P21 and MDM2, and also 
      elevated p53 protein level during sepsis. Pharmacological inhibition of p53 
      partially rescued cell proliferation and apoptotic effects of TNFAIP8 KD. In 
      summary, our work suggests that TNFAIP8 modulates the survival and immune 
      function of Th17 cells after acute insult, which was possibly mediated through 
      the p53/ p21/ MDM2 pathway.
CI  - (c) 2022 Published by Elsevier Ltd.
FAU - Cheng, Xiaobin
AU  - Cheng X
AD  - Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional 
      Chinese Medicine, China.
FAU - Shen, Xiaocheng
AU  - Shen X
AD  - Department of Intensive Care Unit, Wuxi Fifth People's Hospital, China.
FAU - Wang, Min
AU  - Wang M
AD  - Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional 
      Chinese Medicine, China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional 
      Chinese Medicine, China.
FAU - Li, Gang
AU  - Li G
AD  - Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional 
      Chinese Medicine, China.
LA  - eng
PT  - Journal Article
DEP - 20220118
PL  - Netherlands
TA  - Cytokine X
JT  - Cytokine: X
JID - 101743248
PMC - PMC8803581
OTO - NOTNLM
OT  - Immune
OT  - P53
OT  - TNFAIP8
OT  - Th17 cells
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2022/02/08 06:00
MHDA- 2022/02/08 06:01
PMCR- 2022/01/18
CRDT- 2022/02/07 05:37
PHST- 2021/01/12 00:00 [received]
PHST- 2021/09/26 00:00 [revised]
PHST- 2022/01/13 00:00 [accepted]
PHST- 2022/02/07 05:37 [entrez]
PHST- 2022/02/08 06:00 [pubmed]
PHST- 2022/02/08 06:01 [medline]
PHST- 2022/01/18 00:00 [pmc-release]
AID - S2590-1532(22)00001-5 [pii]
AID - 100062 [pii]
AID - 10.1016/j.cytox.2022.100062 [doi]
PST - epublish
SO  - Cytokine X. 2022 Jan 18;4(1):100062. doi: 10.1016/j.cytox.2022.100062. 
      eCollection 2022 Mar.