PMID- 33011290
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20211129
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 76
DP  - 2020 Dec
TI  - Early growth response genes 2 and 3 induced by AP-1 and NF-kappaB modulate TGF-beta1 
      transcription in NK1.1(-) CD4(+) NKG2D(+) T cells.
PG  - 109800
LID - S0898-6568(20)30277-1 [pii]
LID - 10.1016/j.cellsig.2020.109800 [doi]
AB  - NK1.1(-) CD4(+) NKG2D(+) T cells are a subpopulation of regulatory T cells that 
      downregulate the functions of CD4(+) T, CD8(+) T, natural killer (NK) cells, and 
      macrophages through TGF-beta1 production. Early growth response genes 2 (Egr2) and 3 
      (Egr3) maintain immune homeostasis by modulating T lymphocyte development, 
      inhibiting effector T cell function, and promoting the induction of regulatory T 
      cells. Whether Egr2 and Egr3 directly regulate TGF-beta1 transcription in NK1.1(-) 
      CD4(+) NKG2D(+) T cells remains elusive. The expression levels of Egr2 and Egr3 
      were higher in NK1.1(-) CD4(+) NKG2D(+) T cells than in NK1.1(-) CD4(+) NKG2D(-) 
      T cells. Egr2 and Egr3 expression were remarkably increased after stimulating 
      NK1.1(-) CD4(+) NKG2D(+) T cells with sRAE or alpha-CD3/sRAE. The ectopic expression 
      of Egr2 or Egr3 resulted in the enhancement of TGF-beta1 expression, while knockdown 
      of Egr2 or Egr3 led to the decreased expression of TGF-beta1 in NK1.1(-) CD4(+) 
      NKG2D(+) T cells. Egr2 and Egr3 directly bound with the TGF-beta1 promoter as 
      demonstrated by the electrophoretic mobility shift assay and dual-luciferase gene 
      reporter assay. Furthermore, the Egr2 and Egr3 expression of NK1.1(-) CD4(+) 
      NKG2D(+) T cells could be induced by the AP-1 and NF-kappaB transcriptional factors, 
      but had no involvement with the activation of NF-AT and STAT3. In conclusion, 
      Egr2 and Egr3 induced by AP-1 and NF-kappaB directly initiate TGF-beta1 transcription in 
      NK1.1(-) CD4(+) NKG2D(+) T cells. This study indicates that manipulating Egr2 and 
      Egr3 expression would potentiate or alleviate the regulatory function of NK1.1(-) 
      CD4(+) NKG2D(+) T cells and this strategy could be used in the therapy for 
      patients with autoimmune diseases or tumor.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Han, Sen
AU  - Han S
AD  - Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 
      225000, PR China; Vaccine and Immunotherapy Center, Department of Medicine, 
      Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, 
      USA.
FAU - Zhu, Tao
AU  - Zhu T
AD  - Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 
      225000, PR China.
FAU - Ding, Shizhen
AU  - Ding S
AD  - Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 
      225000, PR China.
FAU - Wen, Jianqiang
AU  - Wen J
AD  - Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 
      225000, PR China.
FAU - Lin, Zhijie
AU  - Lin Z
AD  - Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 
      225000, PR China.
FAU - Lu, Guotao
AU  - Lu G
AD  - Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 
      225000, PR China; Department of Gastroenterology, Affiliated Hospital of Yangzhou 
      University, Yangzhou 225000, PR China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Prevention and Treatment of Senile Disease, Yangzhou University, Yangzhou 225000, 
      PR China.
FAU - Xiao, Weiming
AU  - Xiao W
AD  - Department of Gastroenterology, Affiliated Hospital of Yangzhou University, 
      Yangzhou 225000, PR China; Jiangsu Key Laboratory of Integrated Traditional 
      Chinese and Western Medicine for Prevention and Treatment of Senile Disease, 
      Yangzhou University, Yangzhou 225000, PR China.
FAU - Ding, Yanbing
AU  - Ding Y
AD  - Department of Gastroenterology, Affiliated Hospital of Yangzhou University, 
      Yangzhou 225000, PR China; Jiangsu Key Laboratory of Integrated Traditional 
      Chinese and Western Medicine for Prevention and Treatment of Senile Disease, 
      Yangzhou University, Yangzhou 225000, PR China.
FAU - Jia, Xiaoqin
AU  - Jia X
AD  - Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Prevention and Treatment of Senile Disease, Yangzhou University, Yangzhou 225000, 
      PR China; Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA 
      Research, Yangzhou University, Yangzhou 225000, PR China.
FAU - Chen, Huabiao
AU  - Chen H
AD  - Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General 
      Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
FAU - Gong, Weijuan
AU  - Gong W
AD  - Department of Immunology, School of Medicine, Yangzhou University, Yangzhou 
      225000, PR China; Department of Gastroenterology, Affiliated Hospital of Yangzhou 
      University, Yangzhou 225000, PR China; Jiangsu Key Laboratory of Integrated 
      Traditional Chinese and Western Medicine for Prevention and Treatment of Senile 
      Disease, Yangzhou University, Yangzhou 225000, PR China; Jiangsu Key Laboratory 
      of Experimental & Translational Non-coding RNA Research, Yangzhou University, 
      Yangzhou 225000, PR China; Jiangsu Key Laboratory of Zoonosis, Yangzhou 
      University, Yangzhou 225000, PR China. Electronic address: wjgong@yzu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201001
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Egr2 protein, mouse)
RN  - 0 (Egr3 protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 144516-98-3 (Early Growth Response Protein 3)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/immunology
MH  - *CD4-Positive T-Lymphocytes/cytology/immunology
MH  - Early Growth Response Protein 2/*immunology
MH  - Early Growth Response Protein 3/*immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - NF-kappa B/immunology
MH  - Neoplasms/immunology
MH  - Transforming Growth Factor beta1/*immunology
OTO - NOTNLM
OT  - Early growth response gene (Egr)
OT  - NKG2D
OT  - Regulation
OT  - T cells
OT  - TGF-beta1
EDAT- 2020/10/05 06:00
MHDA- 2021/11/30 06:00
CRDT- 2020/10/04 20:23
PHST- 2020/07/08 00:00 [received]
PHST- 2020/09/24 00:00 [revised]
PHST- 2020/09/28 00:00 [accepted]
PHST- 2020/10/05 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2020/10/04 20:23 [entrez]
AID - S0898-6568(20)30277-1 [pii]
AID - 10.1016/j.cellsig.2020.109800 [doi]
PST - ppublish
SO  - Cell Signal. 2020 Dec;76:109800. doi: 10.1016/j.cellsig.2020.109800. Epub 2020 
      Oct 1.