Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps

Neutrophils are essential for immune defense and can respond to infection by releasing chromatin in the form of neutrophil extracellular traps (NETs). Here we show that NETs are induced by mitogens and accompanied by induction of cell-cycle markers, including phosphorylation of the retinoblastoma protein and lamins, nuclear envelope breakdown, and duplication of centrosomes. We identify cyclin-dependent kinases 4 and 6 (CDK4/6) as essential regulators of NETs and show that the response is inhibited by the cell-cycle inhibitor p21Cip. CDK6, in neutrophils, is required for clearance of the fungal pathogen Candida albicans. Our data describe a function for CDK4/6 in immunity. •Neutrophils activate cell-cycle markers when stimulated to make NETs•Cyclin-dependent kinases CDK4/6 regulate NET formation•Cdk6−/− mice have impaired immune response to Candida albicans Neutrophils release chromatin in the form of neutrophil extracellular traps (NETs). Amulic et al. show that NET formation involves activation of cell-cycle markers and identify CDK4/6 as regulators of the process. Cdk6 knockout mice, which are impaired in NET formation, are more susceptible to Candida albicans infection.