Scientists at the University of Texas Southwestern Medical Center and the Scripps Research Institute in California report that an enzyme previously known solely for its role in cell division also acts as an on-off switch in the innate immune system.
The identification of the NEK7 enzyme’s switch-like activity in immunity could lead to new treatments for a variety of medical conditions linked to inflammation via the NRLP3 inflammasome pathway, including certain metabolic disorders, influenza A, gout, atherosclerosis, and possibly some forms of cancer, according to the researchers.
The paper’s lead author is Hexin Shi, Ph.D., a postdoctoral researcher in the Center, who identified the gene for the enzyme and then worked to characterize the enzyme’s role as a new component of the inflammasome.
The research effort marshaled a large team working under one of the NIH’s U19 grants, which are awarded for multidisciplinary research projects such as this one that involve genetics, immunology, physiology, and computational biology.
The researchers genetically screened thousands of mice and conducted exhaustive interdisciplinary experiments: identifying a defect in inflammasome function, ascribing that defect to a mutation in the gene for the NEK7 enzyme, and fully characterizing NEK7 function in innate immunity.
“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,” said Dr. Beutler, who shared the 2011 Nobel Prize in Physiology or Medicine for his work on innate immunity.
The U19 grant is based at Scripps Research Institute near San Diego.