当前位置： SCI文献检索 > BMC IMMUNOLOGY期刊下所有文献 > EGR2 is elevated and positively regulates inflammatory IFNγ production in lupus CD4+ T cells.

EGR2 is elevated and positively regulates inflammatory IFNγ production in lupus CD4+ T cells.

Abstract：

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 IFNγ 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 naïve 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 IFNγ production in lupus effector CD4+ T cells.

journal_name

BMC Immunol

journal_title

BMC immunology

authors

Dai R,Heid B,Xu X,Xie H,Reilly CM,Ahmed SA

doi

10.1186/s12865-020-00370-z

subject

Has Abstract

pub_date

2020-07-09 00:00:00

pages

issue

issn

1471-2172

pii

10.1186/s12865-020-00370-z

journal_volume

pub_type

杂志文章

在线工具

EGR2 is elevated and positively regulates inflammatory IFNγ production in lupus CD4+ T cells.