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CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation

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  • Tiantian Tang

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

  • Xueting Lang

    (University of Science and Technology of China)

  • Congfei Xu

    (University of Science and Technology of China)

  • Xiaqiong Wang

    (University of Science and Technology of China)

  • Tao Gong

    (University of Science and Technology of China)

  • Yanqing Yang

    (University of Science and Technology of China)

  • Jun Cui

    (Sun Yat-sen University)

  • Li Bai

    (University of Science and Technology of China)

  • Jun Wang

    (University of Science and Technology of China)

  • Wei Jiang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Rongbin Zhou

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

Abstract

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.

Suggested Citation

  • Tiantian Tang & Xueting Lang & Congfei Xu & Xiaqiong Wang & Tao Gong & Yanqing Yang & Jun Cui & Li Bai & Jun Wang & Wei Jiang & Rongbin Zhou, 2017. "CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00227-x
    DOI: 10.1038/s41467-017-00227-x
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