The NLRC4 Inflammasome.
The NLRC4 Inflammasome.
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DOI：
10.1111/imr.12607
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发表时间：
2018-01
影响因子：
8.7
通讯作者：
Canna SW
中科院分区：
文献类型：
--
作者：
Duncan JA;Canna SW
15年前，一种最终被称为“炎性体”的炎症信号复合体的基本生物学原理开始被解开，与此同时，许多炎症性疾病也与它的过度活跃有关。虽然家族性地中海热（FMF，导致我在MEFV中发生突变）的基因起源是第一个被发现的，但它与Pyrin炎性体的机制联系是在近20年后才被发现的。在此期间，对NLRP3炎症小体及其过度激活相关疾病的深入研究，在很大程度上决定了炎症小体组成和功能的范式。尽管取得了令人印象深刻的成果，但对NLRP3的关注仍使我们对炎性体生物学的理解存在空白。这些空白中最重要的是炎性小体如何被激活以及炎性小体结构和功能之间的联系。幸运的是，另一种炎性体诱导剂NLRC4的研究填补了这些空白。目前对NLRC4炎症小体的理解可能是对炎症小体范式的最全面的说明：触发器（例如细胞质鞭毛蛋白）、传感器（NAIP）、成核体（NLRC4）、适配器（ASC）和效应体（CASP1）。详细的工作也发现了挑战这一范式的观察结果。同时，每个炎性小体的独特特征提供了一个对比的教训，提供了炎性小体激活、调节和功能的观点。在这篇综述中，我们努力强调NLRC4炎症小体结构和激活的最新突破，在感染和全身炎症中的重要体内工作，以及人类NLRC4相关自身炎症疾病谱的表征。
15 years ago, the fundamental biology of an inflammatory signaling complex eventually dubbed “the inflammasome” began to unravel in chronologic parallel with the discovery that many inflammatory diseases were associated with its hyperactivity. Though the genetic origins of Familial Mediterranean Fever (FMF, caused my mutations in MEFV) were discovered first, it would take nearly two decades before the mechanistic connections to a Pyrin inflammasome were made. In the interim, the intensive study of the NLRP3 inflammasome, and the diseases associated with its hyperactivation, have largely dictated the paradigm of inflammasome composition and function. Despite impressive gains, focusing on NLRP3 left gaps in our understanding of inflammasome biology. Foremost among these gaps were how inflammasomes become activated and the connections between inflammasome structure and function. Fortunately, work in another inflammasome inducer, NLRC4, grew to fill those gaps. The current understanding of the NLRC4 inflammasome is perhaps the most comprehensive illustration of the inflammasome paradigm: trigger (e.g. cytosolic flagellin), sensor (NAIP), nucleator (NLRC4), adaptor (ASC), and effector (CASP1). Detailed work has also identified observations that challenge this paradigm. Simultaneously, the features unique to each inflammasome offer a lesson in contrast, providing perspectives on inflammasome activation, regulation, and function. In this review, we endeavor to highlight recent breakthroughs related to NLRC4 inflammasome structure and activation, important in vivo work in infection and systemic inflammation, and the characterization of a spectrum of human NLRC4-associated autoinflammatory diseases.
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影响因子：
30.5
作者：
Franchi, Luigi;Amer, Amal;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1200195
发表时间：
2012-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cai S;Batra S;Wakamatsu N;Pacher P;Jeyaseelan S
通讯作者：
Jeyaseelan S
影响因子：
64.8
作者：
Kofoed, Eric M.;Vance, Russell E.
通讯作者：
Vance, Russell E.
NLRC4诱导自我繁殖的结构和生化基础
影响因子：
56.9
作者：
Hu, Zehan;Zhou, Qiang;Chai, Jijie
通讯作者：
Chai, Jijie