Gender-dependent expression of murine Irf5 gene: implications for sex bias in autoimmunity.

Gender-dependent expression of murine Irf5 gene: implications for sex bias in autoimmunity.
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小鼠 Irf5 基因的性别依赖性表达:对自身免疫性别偏见的影响。

DOI:
10.1093/jmcb/mjq023
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发表时间:
2010
影响因子:
5.5
通讯作者:
Choubey,Divaker
Choubey,Divaker
中科院分区:
生物学1区
文献类型:
--
作者:
Shen,Hui;Panchanathan,Ravichandran;Rajavelu,Priya;Duan,Xin;Gould,KarenA;Choubey,Divaker

文献摘要

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系统性红斑狼疮(SLE)是一种自身免疫性疾病,其发病过程中导致性别偏见的分子机制尚不清楚。我们发现狼疮易感因子干扰素调节因子5(IRF 5)的表达水平与小鼠性别有关。我们发现,稳态水平的theIrf 5 mRNA相对较高的脾细胞从某些自身免疫易感小鼠(例如,NZB和NZB/W F1)比非自身免疫C57 BL/6小鼠。此外,Irf 5 mRNA和蛋白质水平在女性高于应变和年龄匹配的男性。因此,雌激素受体α(ERα)基因敲除小鼠脾细胞与野生型(ERα+/+)小鼠相比,表达的Irf 5 mRNA水平相对较低,而17β-雌二醇处理的脾细胞表达的Irf 5 mRNA水平升高。此外,来自雌性小鼠的脾B细胞在细胞核中比雄性小鼠具有相对更多的IRF 5蛋白。总的来说,我们的观察结果表明,在表达和亚细胞定位的小鼠IRF 5的性别偏见。
Molecular mechanisms that contribute to sex bias in the development of systemic lupus erythematosus (SLE), an autoimmune disease, remain unknown. We found that the expression levels of interferon regulatory factor 5 (IRF5), a lupus susceptibility factor, depend on gender of mice. We found that steady-state levels of theIrf5mRNA were relatively higher in splenic cells from certain autoimmune-prone mice (for example, NZB and NZB/W F1) than in non-autoimmune C57BL/6 mice. Additionally, levels ofIrf5mRNA and protein were higher in females than in strain and age-matched males. Accordingly, splenic cells from estrogen receptor-alpha (ERα) knockout, when compared with the wild-type (ERα+/+), female mice expressed relatively lower levels ofIrf5mRNA and the treatment of splenic cells with 17β-estradiol increased the levels. Furthermore, splenic B cells from the female mice had relatively more IRF5 protein in the nucleus than the male mice. Collectively, our observations demonstrate a gender bias in the expression and sub-cellular localization of the murine IRF5.