NLRC3, a Member of the NLR Family of Proteins, Is a Negative Regulator of Innate Immune Signaling Induced by the DNA Sensor STING

doi:10.1016/j.immuni.2014.01.010

	NLRC3, a Member of the NLR Family of Proteins, Is a Negative Regulator of Innate Immune Signaling Induced by the DNA Sensor STING
	Zhang, Lu 1,2; Mo, Jinyao 3; Swanson, Karen V.1; Wen, Haitao 1; Petrucelli, Alex 1; Gregory, Sean M.1; Zhang, Zhigang 1; Schneider, Monika 4; Jiang, Yan 7; Fitzgerald, Katherine A.8; Ouyang, Songying 7; Liu, Zhi-Jie9 ; Damania, Blossom 1,4; Shu, Hong-Bing 10; Duncan, Joseph A.3; Ting, Jenny P. -Y.1,4,5,6
	2014-03-20
发表期刊	IMMUNITY (IF:25.5[JCR-2023],33.2[5-Year])
ISSN	1074-7613
卷号	40 期号:3 页码:329-341
发表状态	已发表
DOI	10.1016/j.immuni.2014.01.010
摘要	Stimulator of interferon genes (STING, also named MITA, MYPS, or ERIS) is an intracellular DNA sensor that induces type I interferon through its interaction with TANK-binding kinase 1 (TBK1). Here we found that the nucleotide-binding, leucine-rich-repeat-containing protein, NLRC3, reduced STING-dependent innate immune activation in response to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses. NLRC3 associated with both STING and TBK1 and impeded STING-TBK1 interaction and downstream type I interferon production. By using purified recombinant proteins, we found NLRC3 to interact directly with STING. Furthermore, NLRC3 prevented proper trafficking of STING to perinuclear and punctated region, known to be important for its activation. In animals, herpes simplex virus 1 (HSV-1)-infected Nlrc3(-/-) mice exhibited enhanced innate immunity and reduced morbidity and viral load. This demonstrates the intersection of two key pathways of innate immune regulation, NLR and STING, to fine tune host response to intracellular DNA, DNA virus, and c-di-GMP.
收录类别	SCI
语种	英语
资助项目	NSFC[31200559] ; NSFC[31330019]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000333422300007
出版者	CELL PRESS
WOS关键词	NF-KAPPA-B ; CYCLIC DI-GMP ; CYTOSOLIC DNA ; COLON INFLAMMATION ; ADAPTER ; RECOGNITION ; ACTIVATION ; RESPONSES ; VIRUS ; TRAF6
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1069
专题	iHuman研究所_PI研究组_刘志杰组 iHuman研究所
通讯作者	Ting, Jenny P. -Y.
作者单位	1.Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA 2.Univ N Carolina, Dept Oral Biol, Sch Dent, Chapel Hill, NC 27599 USA 3.Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC 27599 USA 4.Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA 5.Univ N Carolina, Inst Inflammatory Dis, Chapel Hill, NC 27599 USA 6.Univ N Carolina, Ctr Translat Immunol, Chapel Hill, NC 27599 USA 7.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 8.Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA 9.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 10.Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Lu,Mo, Jinyao,Swanson, Karen V.,et al. NLRC3, a Member of the NLR Family of Proteins, Is a Negative Regulator of Innate Immune Signaling Induced by the DNA Sensor STING[J]. IMMUNITY,2014,40(3):329-341.
APA	Zhang, Lu.,Mo, Jinyao.,Swanson, Karen V..,Wen, Haitao.,Petrucelli, Alex.,...&Ting, Jenny P. -Y..(2014).NLRC3, a Member of the NLR Family of Proteins, Is a Negative Regulator of Innate Immune Signaling Induced by the DNA Sensor STING.IMMUNITY,40(3),329-341.
MLA	Zhang, Lu,et al."NLRC3, a Member of the NLR Family of Proteins, Is a Negative Regulator of Innate Immune Signaling Induced by the DNA Sensor STING".IMMUNITY 40.3(2014):329-341.