Spliceosomal GTPase Eftud2 regulates microglial activation and polarization

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...

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Main Authors: Guo-Chao Yang, Yuan Shi, Chao-Nan Fan, Ying Li, Meng-Qi Yuan, Jie Pei, Yan Wu, Hai-Tao Wu
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2023-01-01
Series:Neural Regeneration Research
Subjects:
Online Access:http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=856;epage=862;aulast=Yang
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author Guo-Chao Yang
Yuan Shi
Chao-Nan Fan
Ying Li
Meng-Qi Yuan
Jie Pei
Yan Wu
Hai-Tao Wu
author_facet Guo-Chao Yang
Yuan Shi
Chao-Nan Fan
Ying Li
Meng-Qi Yuan
Jie Pei
Yan Wu
Hai-Tao Wu
author_sort Guo-Chao Yang
collection DOAJ
description 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.
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spelling doaj.art-6f0e2978f7324600a9e53fd53101b04b2022-12-22T04:12:36ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-0118485686210.4103/1673-5374.347739Spliceosomal GTPase Eftud2 regulates microglial activation and polarizationGuo-Chao YangYuan ShiChao-Nan FanYing LiMeng-Qi YuanJie PeiYan WuHai-Tao WuElongation 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=856;epage=862;aulast=Yangalzheimer’s disease; anti-inflammatory phenotype; bv2; eftud2; inflammation; lipopolysaccharide; microglia; nuclear factor-kappab; proinflammatory phenotype; spliceosomal gtpase
spellingShingle Guo-Chao Yang
Yuan Shi
Chao-Nan Fan
Ying Li
Meng-Qi Yuan
Jie Pei
Yan Wu
Hai-Tao Wu
Spliceosomal GTPase Eftud2 regulates microglial activation and polarization
Neural Regeneration Research
alzheimer’s disease; anti-inflammatory phenotype; bv2; eftud2; inflammation; lipopolysaccharide; microglia; nuclear factor-kappab; proinflammatory phenotype; spliceosomal gtpase
title Spliceosomal GTPase Eftud2 regulates microglial activation and polarization
title_full Spliceosomal GTPase Eftud2 regulates microglial activation and polarization
title_fullStr Spliceosomal GTPase Eftud2 regulates microglial activation and polarization
title_full_unstemmed Spliceosomal GTPase Eftud2 regulates microglial activation and polarization
title_short Spliceosomal GTPase Eftud2 regulates microglial activation and polarization
title_sort spliceosomal gtpase eftud2 regulates microglial activation and polarization
topic alzheimer’s disease; anti-inflammatory phenotype; bv2; eftud2; inflammation; lipopolysaccharide; microglia; nuclear factor-kappab; proinflammatory phenotype; spliceosomal gtpase
url http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=856;epage=862;aulast=Yang
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AT yingli spliceosomalgtpaseeftud2regulatesmicroglialactivationandpolarization
AT mengqiyuan spliceosomalgtpaseeftud2regulatesmicroglialactivationandpolarization
AT jiepei spliceosomalgtpaseeftud2regulatesmicroglialactivationandpolarization
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