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 PMID:26642356  

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

Hexin Shi | Ying Wang | Xiaohong Li | Xiaoming Zhan | Miao Tang | Maggy Fina | Lijing Su | David Pratt | Chun Hui Bu | Sara Hildebrand | Stephen Lyon | Lindsay Scott | Jiexia Quan | Qihua Sun | Jamie Russell | Stephanie Arnett | Peter Jurek | Ding Chen | Vladimir V Kravchenko | John C Mathison | Eva Marie Y Moresco | Nancy L Monson | Richard J Ulevitch | Bruce Beutler
Nature immunology | 2016

The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1β (IL-1β) 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.

Pubmed ID: 26642356

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: U19 AI100627

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