Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (4): 856-862.doi: 10.4103/1673-5374.347739

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Spliceosomal GTPase Eftud2 regulates microglial activation and polarization

Guo-Chao Yang1, Yuan Shi2, Chao-Nan Fan2, Ying Li2, Meng-Qi Yuan3, Jie Pei4, Yan Wu2, Hai-Tao Wu1, 2, 5, *   

  1. 1School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China;  2Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, China;  3Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, Hunan Province, China;  4School of Basic Medicine, Anhui Medical University, Hefei, Anhui Province, China;  5Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2023-04-15 Published:2022-10-29
  • Contact: Hai-Tao Wu, PhD, wuht@bmi.ac.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 32171148, 31770929, 31522029 (all to HTW); the National Key Research and Development Program of China, Nos. 2021ZD0202500, 2021YFA1101801 (both to HTW); and a grant from Beijing Commission of Science and Technology of China, Nos. Z181100001518001, Z161100000216154 (both to HTW). 

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Abstract: 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.

Key words: Alzheimer’s disease, anti-inflammatory phenotype, BV2, Eftud2, inflammation, lipopolysaccharide, microglia, nuclear factor-kappaB, proinflammatory phenotype, spliceosomal GTPase