NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component

被引：593

作者：

Shi, Hexin ^{[1
]}

Wang, Ying ^{[1
]}

Li, Xiaohong ^{[1
]}

Zhan, Xiaoming ^{[1
]}

Tang, Miao ^{[1
]}

Fina, Maggy ^{[1
]}

Su, Lijing ^{[1
]}

Pratt, David ^{[1
]}

Bu, Chun Hui ^{[1
]}

Hildebrand, Sara ^{[1
]}

Lyon, Stephen ^{[1
]}

Scott, Lindsay ^{[1
]}

Quan, Jiexia ^{[1
]}

Sun, Qihua ^{[1
]}

Russell, Jamie ^{[1
]}

Arnett, Stephanie ^{[1
]}

Jurek, Peter ^{[1
]}

Chen, Ding ^{[2
]}

Kravchenko, Vladimir V. ^{[3
]}

Mathison, John C. ^{[3
]}

Marie Y Moresco, Eva ^{[1
]}

Monson, Nancy L. ^{[2
]}

Ulevitch, Richard J. ^{[3
]}

Beutler, Bruce ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Ctr Genet Host Def, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA

[3] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 03期

基金：

美国国家卫生研究院;

关键词：

CELL-DEATH; KINASE; ENCEPHALOMYELITIS; MITOCHONDRIA; CENTROSOME;

D O I：

10.1038/ni.3333

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1 beta (IL-1 beta) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.

引用

页码：250 / 258

页数：9

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