PMID- 32646370
OWN - NLM
STAT- MEDLINE
DCOM- 20210812
LR  - 20210812
IS  - 1471-2172 (Electronic)
IS  - 1471-2172 (Linking)
VI  - 21
IP  - 1
DP  - 2020 Jul 9
TI  - EGR2 is elevated and positively regulates inflammatory IFNgamma production in lupus 
      CD4(+) T cells.
PG  - 41
LID - 10.1186/s12865-020-00370-z [doi]
LID - 41
AB  - BACKGROUND: Recent studies have shown that early growth response 2 (EGR2) is 
      highly induced in activated T cells and regulates T cell functions. In normal 
      C57BL/6 (B6) mice, deletion of EGR2 in lymphocytes results in the development of 
      lupus-like systemic autoimmune disease, which implies indirectly an autoimmune 
      protective role of EGR2. Conversely, increased EGR2 gene expression is suggested 
      to link with high risk of human lupus. In the present studies we sought to 
      clarify the expression and inflammation regulatory role of EGR2 in murine lupus T 
      cells directly. RESULTS: We performed RT-qPCR analysis and found a significant 
      increase of EGR2 mRNA expression in human lupus PBMCs and in CD4(+) T cells from 
      three different murine lupus models including MRL-lpr, B6-lpr, and B6.sle123 mice 
      at diseased stage when compared to age-matched control MRL or B6 mice. By 
      performing intracellular flow cytometry analysis, we found that EGR2 protein 
      expression was significantly increased in resting lupus (either MRL-lpr or 
      B6.sle123) CD4(+) T cells when compared to CD4(+) T cells from their respective 
      non-autoimmune controls. However, there was no difference of EGR2 protein 
      expression in anti-CD3 and anti-CD28 stimulated control and lupus CD4(+) T cells 
      since there was a stronger induction of EGR2 in activated control CD4(+) T cells. 
      EGR2 expression was significantly increased in MRL-lpr mice at an age when lupus 
      is manifested. To understand further the function of elevated EGR2 in lupus 
      CD4(+) T cells, we inhibited EGR2 with a specific siRNA in vitro in splenocytes 
      from MRL-lpr and control MRL mice at 15 weeks-of-age. We found that EGR2 
      inhibition significantly reduced IFNgamma production in PMA and ionomycin activated 
      MRL-lpr lupus CD4(+) T cells, but not control MRL CD4(+) T cells. We also found 
      that inhibition of EGR2 in vitro suppressed the Th1 differentiation in both MRL 
      and MRL-lpr naive CD4(+) T cells. CONCLUSIONS: EGR2 is highly upregulated in 
      human and murine lupus cells. Our in vitro data suggest a positive role of EGR2 
      in the regulation of Th1 differentiation and IFNgamma production in lupus effector 
      CD4(+) T cells.
FAU - Dai, Rujuan
AU  - Dai R
AUID- ORCID: 0000-0002-1074-8974
AD  - Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of 
      Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA. rdai05@vt.edu.
FAU - Heid, Bettina
AU  - Heid B
AD  - Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of 
      Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
FAU - Xu, Xiguang
AU  - Xu X
AD  - Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
AD  - Fralin Life Sciences Institute at Virginia Tech, Blacksburg, VA, USA.
FAU - Xie, Hehuang
AU  - Xie H
AD  - Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of 
      Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
AD  - Fralin Life Sciences Institute at Virginia Tech, Blacksburg, VA, USA.
FAU - Reilly, Christopher M
AU  - Reilly CM
AD  - Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of 
      Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
AD  - Edward Via College of Osteopathic Medicine, Blacksburg, VA, USA.
FAU - Ahmed, S Ansar
AU  - Ahmed SA
AD  - Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of 
      Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA. ansrahmed@vt.edu.
LA  - eng
GR  - 460125/Edward Via College of Osteopathic Medicine (VCOM)-Virginia-Maryland 
      College of Veterinary Medicine (VMCVM)/International
GR  - 176979/Virginia-Maryland College of Veterinary Medicine/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200709
PL  - England
TA  - BMC Immunol
JT  - BMC immunology
JID - 100966980
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Egr2 protein, mouse)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Early Growth Response Protein 2/genetics/*metabolism
MH  - Humans
MH  - Inflammation/immunology/*metabolism
MH  - Interferon-gamma/metabolism
MH  - Lupus Erythematosus, Systemic/immunology/*metabolism
MH  - Lupus Nephritis/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred MRL lpr
MH  - Mice, Knockout
MH  - Up-Regulation
PMC - PMC7346656
OTO - NOTNLM
OT  - EGR2
OT  - IFNgamma
OT  - Inflammation
OT  - Lupus
OT  - Th1
COIS- The authors declare no competing interests.
EDAT- 2020/07/11 06:00
MHDA- 2021/08/13 06:00
PMCR- 2020/07/09
CRDT- 2020/07/11 06:00
PHST- 2020/03/16 00:00 [received]
PHST- 2020/06/30 00:00 [accepted]
PHST- 2020/07/11 06:00 [entrez]
PHST- 2020/07/11 06:00 [pubmed]
PHST- 2021/08/13 06:00 [medline]
PHST- 2020/07/09 00:00 [pmc-release]
AID - 10.1186/s12865-020-00370-z [pii]
AID - 370 [pii]
AID - 10.1186/s12865-020-00370-z [doi]
PST - epublish
SO  - BMC Immunol. 2020 Jul 9;21(1):41. doi: 10.1186/s12865-020-00370-z.