CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.
CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.
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CLICs 依赖性氯离子流出是 NLRP3 炎性体激活的重要且近端上游事件。
DOI：
10.1038/s41467-017-00227-x
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发表时间：
2017-08-04
影响因子：
16.6
通讯作者：
Zhou R
中科院分区：
文献类型：
--
作者：
Tang T;Lang X;Xu C;Wang X;Gong T;Yang Y;Cui J;Bai L;Wang J;Jiang W;Zhou R
NLRP3炎症体可以感知不同的病原体或危险信号，据报道参与了许多人类疾病的发生。钾外流和线粒体损伤都被报道介导了NLRP3炎症体的激活，但潜在的、协调的信号事件仍不清楚。在这里，我们发现氯离子细胞内通道(CLIC)作用于钾离子外流-线粒体活性氧簇(ROS)轴的下游，从而促进NLRP3炎症体的激活。NLRP3激动剂诱导钾外流，导致线粒体损伤和ROS的产生。然后，线粒体ROS诱导CLICs移位到质膜，诱导氯离子外流，促进NEK7-NLRP3相互作用、炎症体组装、caspase-1激活和IL-1β分泌。因此，我们的结果确认ClICS依赖的氯离子外流是NLRP3激活的一个重要的和近端的上游事件。NLRP3炎症体是调节针对病原体或应激的天然免疫的关键，但潜在的信号调节仍不清楚。在这里，作者展示了氯细胞内通道(CLIC)在线粒体应激和炎性小体激活之间的接口，以调节炎症反应。
The NLRP3 inflammasome can sense different pathogens or danger signals, and has been reported to be involved in the development of many human diseases. Potassium efflux and mitochondrial damage are both reported to mediate NLRP3 inflammasome activation, but the underlying, orchestrating signaling events are still unclear. Here we show that chloride intracellular channels (CLIC) act downstream of the potassium efflux-mitochondrial reactive oxygen species (ROS) axis to promote NLRP3 inflammasome activation. NLRP3 agonists induce potassium efflux, which causes mitochondrial damage and ROS production. Mitochondrial ROS then induces the translocation of CLICs to the plasma membrane for the induction of chloride efflux to promote NEK7–NLRP3 interaction, inflammasome assembly, caspase-1 activation, and IL-1β secretion. Thus, our results identify CLICs-dependent chloride efflux as an essential and proximal upstream event for NLRP3 activation. The NLRP3 inflammasome is key to the regulation of innate immunity against pathogens or stress, but the underlying signaling regulation is still unclear. Here the authors show that chloride intracellular channels (CLIC) interface between mitochondria stress and inflammasome activation to modulate inflammatory responses.
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影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
影响因子：
16.6
作者：
Daniels MJ;Rivers-Auty J;Schilling T;Spencer NG;Watremez W;Fasolino V;Booth SJ;White CS;Baldwin AG;Freeman S;Wong R;Latta C;Yu S;Jackson J;Fischer N;Koziel V;Pillot T;Bagnall J;Allan SM;Paszek P;Galea J;Harte MK;Eder C;Lawrence CB;Brough D
通讯作者：
Brough D
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1073/pnas.1201351109
发表时间：
2012-04-17
影响因子：
11.1
作者：
Malik, Mariam;Jividen, Kasey;Yuspa, Stuart H.
通讯作者：
Yuspa, Stuart H.