Elongation factor Tu GTP binding domain protein 2 (Eftud2) is a spliceosomal GTPase that serves as an innate immune modulator restricting virus infection. Microglia are the resident innate immune cells and the key players of immune response in the central nervous system. However, the role of Eftud2 in microglia has not been reported. In this study, we performed immunofluorescent staining and western blot assay and found that Eftud2 was upregulated in microglia of a 5xFAD transgenic mouse model of Alzheimer's disease. Next, we generated an inducible microglia-specific Eftud2 conditional knockout mouse line (CX3CR1-CreER; Eftud2f/f cKO) via Cre/loxP recombination and found that Eftud2 deficiency resulted in abnormal proliferation and promoted anti-inflammatory phenotype activation of microglia. Furthermore, we knocked down Eftud2 in BV2 microglia with siRNA specifically targeting Eftud2 and found that Eftud2-mediated regulation of microglial proinflammatory/anti-inflammatory phenotype activation in response to inflammation might be dependent on the NF-κB signaling pathway. Our findings suggest that Eftud2 plays a key role in regulating microglial polarization and homeostasis possibly through the NF-κB signaling pathway.

中文翻译：

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剪接体 GTPase Eftud2 调节小胶质细胞的激活和极化。

延伸因子 Tu GTP 结合结构域蛋白 2 (Eftud2) 是一种剪接体 GTP 酶，可作为限制病毒感染的先天免疫调节剂。小胶质细胞是常驻的先天免疫细胞，是中枢神经系统免疫反应的关键参与者。然而，Eftud2 在小胶质细胞中的作用尚未见报道。在这项研究中，我们进行了免疫荧光染色和蛋白质印迹分析，发现 Eftud2 在阿尔茨海默病 5xFAD 转基因小鼠模型的小胶质细胞中上调。接下来，我们通过 Cre/loxP 重组生成了可诱导的小胶质细胞特异性 Eftud2 条件性敲除小鼠系（CX3CR1-CreER；Eftud2f/f cKO），发现 Eftud2 缺陷导致异常增殖并促进小胶质细胞的抗炎表型激活。此外，我们用特异性靶向 Eftud2 的 siRNA 敲低了 BV2 小胶质细胞中的 Eftud2，发现 Eftud2 介导的小胶质细胞促炎/抗炎表型激活对炎症反应的调节可能依赖于 NF-κB 信号通路。我们的研究结果表明，Eftud2 可能通过 NF-κB 信号通路在调节小胶质细胞极化和稳态中发挥关键作用。