Neutrophil extracellular traps can serve as platforms for processing and activation of IL ‐1 family cytokines

Activated neutrophils can undergo a mode of regulated cell death, called NET osis, that results in the extrusion of chromatin into the extracellular space, thereby acting as extracellular traps for microorganisms. Neutrophil‐derived extracellular traps ( NET s) are comprised of DNA decorated with histones, antimicrobial proteins and neutrophil granule proteases, such as elastase and cathepsin G (Cat G). NET ‐associated factors are thought to enhance the antimicrobial properties of these structures and localisation of antimicrobial molecules on NET s may serve to increase their local concentration. Because neutrophil‐derived proteases have been implicated in the processing and activation of several members of the extended interleukin ( IL )‐1 family, we wondered whether neutrophil NET s could also serve as platforms for the activation of proinflammatory cytokines. Here, we show that neutrophil NET s potently processed and activated IL ‐1α as well as IL ‐36 subfamily cytokines through NET ‐associated Cat G and elastase. Thus, in addition to their role as antimicrobial traps, NET s can also act as local sites of cytokine processing and activation.