Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA.
J Mol Cell Biol. 2010 Oct;2(5):284-90. doi: 10.1093/jmcb/mjq023. Epub 2010 Aug 27.
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 the Irf5 mRNA were relatively higher in splenic cells from certain autoimmune-prone mice (for example, NZB and NZB/W F(1)) than in non-autoimmune C57BL/6 mice. Additionally, levels of Irf5 mRNA 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 of Irf5 mRNA 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.
导致系统性红斑狼疮（SLE）这种自身免疫性疾病出现性别偏向的分子机制尚不清楚。我们发现，狼疮易感性因子干扰素调节因子 5（IRF5）的表达水平取决于小鼠的性别。我们发现，某些自身免疫倾向的小鼠（例如 NZB 和 NZB/W F(1)）的脾细胞中 Irf5 mRNA 的稳态水平相对高于非自身免疫性 C57BL/6 小鼠。此外，IRF5mRNA 和蛋白水平在雌性小鼠中高于同品系和年龄匹配的雄性小鼠。相应地，与野生型（ERα(+/+)）雌性小鼠相比，雌激素受体-α（ERα）敲除小鼠的脾细胞中 Irf5 mRNA 的表达水平相对较低，并且用 17β-雌二醇处理脾细胞会增加其水平。此外，雌性小鼠的脾 B 细胞的细胞核中 IRF5 蛋白的含量也高于雄性小鼠。总的来说，我们的观察结果表明，IRF5 在表达和亚细胞定位方面存在性别偏向。
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