NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens
NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens
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NLRC5 调节宿主防御细胞内病原体的 MHC I 类抗原呈递
DOI：
10.1038/cr.2012.56
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发表时间：
2012-04
期刊：
影响因子：
44.1
通讯作者：
Qian, Youcun
中科院分区：
文献类型：
--
作者：
Zhu, Shu;Leng, Qibin;Leng, Qibin;Wang, Hongyan;Wang, Hongyan;Shi, Yufang;Shi, Yufang;Qian, Youcun;Qian, Youcun
nod样受体（NLRs）是一个细胞内蛋白家族，在抗微生物感染的先天免疫中起关键作用。NLRC5是NLR家族中最大的成员，最近引起了人们的广泛关注。然而，关于NLRC5在宿主防御和调节免疫信号通路中的作用，体外研究报告的结果不一致。NLRC5在体内的功能尚不清楚。在这里，我们报道NLRC5在体内是宿主防御细胞内病原体的关键调节因子。NLRC5对于参与MHC I类抗原呈递的基因的表达是特别需要的。nlrc5缺陷小鼠表现出MHC I类基因表达的严重缺陷，并伴有激活L. monocytogenes特异性CD8+ T细胞反应的失败，包括激活、增殖和细胞毒性，突变小鼠更容易受到病原体感染。nlrc5缺陷小鼠中nlrp3介导的炎性体激活也部分受损。然而，NLRC5在病原体诱导的NF-κ b依赖性促炎基因和I型干扰素基因的表达中是必不可少的。因此，NLRC5通过调控MHC I类抗原呈递来控制细胞内病原体感染。
NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection. NLRC5, the largest member of the NLR family, has recently attracted much attention. However, in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways. The in vivo function of NLRC5 remains unknown. Here, we report that NLRC5 is a critical regulator of host defense against intracellular pathogens in vivo. NLRC5 was specifically required for the expression of genes involved in MHC class I antigen presentation. NLRC5-deficient mice showed a profound defect in the expression of MHC class I genes and a concomitant failure to activate L. monocytogenes-specific CD8+ T cell responses, including activation, proliferation and cytotoxicity, and the mutant mice were more susceptible to the pathogen infection. NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice. However, NLRC5 was dispensable for pathogen-induced expression of NF-κB-dependent pro-inflammatory genes as well as type I interferon genes. Thus, NLRC5 critically regulates MHC class I antigen presentation to control intracellular pathogen infection.
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影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
DOI：
10.1038/nri2851
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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通过 TRAF3 介导的白细胞介素 17 受体信号抑制调节实验性自身免疫性脑脊髓炎
DOI：
10.1084/jem.20100703
发表时间：
2010-11-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Zhu S;Pan W;Shi P;Gao H;Zhao F;Song X;Liu Y;Zhao L;Li X;Shi Y;Qian Y
通讯作者：
Qian Y
DOI：
10.4049/jimmunol.1003111
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Davis BK;Roberts RA;Huang MT;Willingham SB;Conti BJ;Brickey WJ;Barker BR;Kwan M;Taxman DJ;Accavitti-Loper MA;Duncan JA;Ting JP
通讯作者：
Ting JP
影响因子：
4.4
作者：
Benko, Szilvia;Magalhaes, Joao G.;Girardin, Stephen E.
通讯作者：
Girardin, Stephen E.