Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation

Acute inflammation, characterized by a rapid influx of neutrophils, is a protective response that can lead to chronic inflammatory diseases when left unresolved. We previously showed that secretion of LTB₄-containing exosomes via nuclear envelope-derived multivesicular bodies is required for effective neutrophil infiltration during inflammation. Here we report that the co-secretion of these exosomes with nuclear DNA facilitates the resolution of the neutrophil infiltrate in a mouse skin model of sterile inflammation. Activated neutrophils exhibit rapid and repetitive DNA secretion as they migrate directionally using a mechanism distinct from suicidal neutrophil extracellular trap release and cell death. Packaging of DNA in the lumen of nuclear envelope-multivesicular bodies is mediated by lamin B receptor and chromatin decondensation. These findings advance our understanding of neutrophil functions during inflammation and the physiological relevance of DNA secretion.