Cholesterol crystals trigger neutrophil extracellular trap (NET) formation, which primes macrophages and Th17 cells for cytokine production in atherosclerosis. In atherosclerosis, macrophages release interleukin-1β (IL-1β), a key driver of inflammation, through two steps: priming signals that promote IL-1β transcription and danger signals that activate inflammasomes to process IL-1β for secretion. Cholesterol crystals act as both priming and danger signals, triggering neutrophils to release NETs. These NETs prime macrophages for cytokine release, activating Th17 cells that amplify immune cell recruitment in atherosclerotic plaques. NETs also enhance the production of IL-1β and IL-17, which drive inflammation and atherosclerosis. The study shows that NETs are essential for the transcription of pro-inflammatory cytokines and that their absence reduces atherosclerosis plaque size. NETs also promote the recruitment of neutrophils and Th17 cells, contributing to chronic sterile inflammation. The findings suggest that NETs play a critical role in atherosclerosis by modulating cytokine production and immune cell activation.Cholesterol crystals trigger neutrophil extracellular trap (NET) formation, which primes macrophages and Th17 cells for cytokine production in atherosclerosis. In atherosclerosis, macrophages release interleukin-1β (IL-1β), a key driver of inflammation, through two steps: priming signals that promote IL-1β transcription and danger signals that activate inflammasomes to process IL-1β for secretion. Cholesterol crystals act as both priming and danger signals, triggering neutrophils to release NETs. These NETs prime macrophages for cytokine release, activating Th17 cells that amplify immune cell recruitment in atherosclerotic plaques. NETs also enhance the production of IL-1β and IL-17, which drive inflammation and atherosclerosis. The study shows that NETs are essential for the transcription of pro-inflammatory cytokines and that their absence reduces atherosclerosis plaque size. NETs also promote the recruitment of neutrophils and Th17 cells, contributing to chronic sterile inflammation. The findings suggest that NETs play a critical role in atherosclerosis by modulating cytokine production and immune cell activation.