In a new study, researchers at UT Southwestern Medical Center in Texas and The Scripps Research Institute in California discovered that the enzyme NEK7, vital to cell division, plays a crucial role in the activation of the NLRP3 inflammasome, essential to the onset of inflammation. This discovery may have a significant impact in therapy research for a number of diseases related to inflammation, including multiple sclerosis (MS). The research paper, entitled “NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component,” was published in the journal Nature Immunology.
The NLRP3 inflammasome, after assembly into a multiprotein structure complex, activates and amplifies inflammatory pathways to fight infection in response to microbes and other dangerous signals by activating proinflammatory cytokines such as interleukin 1β (IL-1β) and IL-18.
The team of researchers, funded by one of the National Institutes of Health’s U19 grants, used mice models of inflammatory bowel disease (IBD) and MS to identified a defect in the inflammasome function, and were able to connect it to a mutation in the gene encoding the NEK7 enzyme. This discovery led to a full characterization of the role of NEK7 in the innate immunity and the inflammatory process.
NEK7 was previously only known to participate in mitosis (cell division), a process by which the cell nucleus of a parent cell divides to allow the generation of two new daughter cells, with their own complete full set of genes. Researchers observed that NEK7 promoted the NLRP3-dependent cellular inflammatory response that led to the onset of experimental autoimmune encephalitis (EAE) in mice, a condition that mimics MS in humans.
Study’s senior author Dr. Bruce Beutler, Nobel laureate and director of the Center for the Genetics of Host Defense at UT Southwestern, said of the results in a press release, “Our work has shown that the inflammasome cannot become activated during mitosis. This is possibly a protective mechanism that prevents damage to DNA during this part of the cell cycle.”
Researchers theorized that the findings suggest that NEK7 exerts a mutually exclusive role as a cellular “on-off switch” both in the inflammasome response and in cell division, raising the possibility of new treatments for conditions linked to inflammation via the NRLP3 inflammasome pathway.