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

By Hexin Shi, Ying Wang, Xiaohong Li, X. Zhan, M. Tan, Maggy W Fina, L. Su, David Pratt, C. Bu, Sara Hildebrand and 14 more. Nature Immunology, 2015

678 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2ccb464e026c30976a005dc61078d817aedf58fc

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In Immunology

1. G. Núñez
2. H. Hara
3. Rongbin Zhou
4. Yuan He

In Molecular Biology

1. Yuan He
2. H. Hara
3. G. Núñez
4. Wei Jiang
5. Rongbin Zhou
6. C. A. Dinarello
7. J. Tschopp

Citations in the corpus

• The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation (2019, background): “Three in vivo models have further demonstrated the critical role for Nek7 in NLRP3 inflammasome activation [168,170].”
• Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders (2017, background): “In addition, NEK7, another component of NLRP3 complex (He et al., 2016; 3225JEM Vol. 214, No. 11 Schmid-Burgk et al., 2016; Shi et al., 2016), was also not pulled down (Fig.”
• Mechanism and regulation of NLRP3 inflammasome activation (2016, background): “Furthermore, the kinase activity of Nek7 is also not required for Nek7mediated NLRP3 activation [77,78].”
• Nek7 is an essential mediator of NLRP3 activation downstream of potassium efflux (2016, neutral): “Our results are in agreement with recent studies that identified Nek7 as a critical regulator of the NLRP3 inflammasome 29,30 .”