Spliceosomal GTPase Eftud2 regulates microglial activation and polarization

• Published in: Neural regeneration research Vol. 18; no. 4; pp. 856 - 862
• Main Authors: Yang, Guo-Chao, Shi, Yuan, Fan, Chao-Nan, Li, Ying, Yuan, Meng-Qi, Pei, Jie, Wu, Yan, Wu, Hai-Tao
• Format: Journal Article
• Language: English
• Published: Mumbai Wolters Kluwer India Pvt. Ltd 01.04.2023; Medknow Publications & Media Pvt. Ltd; School of Basic Medicine,Qingdao University,Qingdao,Shandong Province,China%Department of Neurobiology,Beijing Institute of Basic Medical Sciences,Beijing,China%Institute of Neuroscience,Hengyang Medical College,University of South China,Hengyang,Hunan Province,China%School of Basic Medicine,Anhui Medical University,Hefei,Anhui Province,China%School of Basic Medicine,Qingdao University,Qingdao,Shandong Province,China; Department of Neurobiology,Beijing Institute of Basic Medical Sciences,Beijing,China; Key Laboratory of Neuroregeneration,Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Alzheimer's disease; alzheimer’s disease; anti-inflammatory phenotype; bv2; eftud2; inflammation; lipopolysaccharide; microglia; nuclear factor-kappab; proinflammatory phenotype; spliceosomal gtpase; Rodents; Eftud2; proinflammatory phenotype; inflammation; spliceosomal GTPase; anti-inflammatory phenotype; nuclear factor-kappaB; lipopolysaccharide; Alzheimer's disease; microglia; BV2
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.347739

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.