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 (NE)-derived multivesicular bodies (MVBs) 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 (NET) release and cell death. Packaging of DNA in the lumen of NE-MVBs is mediated by lamin B receptor (LBR) and chromatin decondensation. These findings advance our understanding of neutrophil functions during inflammation and the physiological significance of DNA secretion.