Spliceosomal GTPase Eftud2 regulates microglial activation and polarization  

作　　者：Guo-Chao Yang Yuan Shi Chao-Nan Fan Ying Li Meng-Qi Yuan Jie Pei Yan Wu Hai-Tao Wu 

机构地区：[1]School of Basic Medicine,Qingdao University,Qingdao,Shandong Province,China [2]Department of Neurobiology,Beijing Institute of Basic Medical Sciences,Beijing,China [3]Institute of Neuroscience,Hengyang Medical College,University of South China,Hengyang,Hunan Province,China [4]School of Basic Medicine,Anhui Medical University,Hefei,Anhui Province,China [5]Key Laboratory of Neuroregeneration,Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2023年第4期856-862,共7页中国神经再生研究（英文版）

基　　金：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);a grant from Beijing Commission of Science and Technology of China,Nos.Z181100001518001,Z161100000216154(both to HTW)。

摘　　要：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;Eftud2^(f/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.

关 键 词：Alzheimer’s disease anti-inflammatory phenotype BV2 Eftud2 inflammation LIPOPOLYSACCHARIDE MICROGLIA nuclear factor-kappaB proinflammatory phenotype spliceosomal GTPase 

分 类 号：R741[医药卫生—神经病学与精神病学]