Myeloid-derived growth factor regulates neutrophil motility in interstitial tissue damage

Neutrophil recruitment to tissue damage is essential for host defense but can also impede tissue repair. The cues that differentially regulate neutrophil responses to tissue damage and infection remain unclear. Here, we report that the paracrine factor myeloid-derived growth factor (MYDGF) is induced by tissue damage and regulates neutrophil motility to damaged, but not infected, tissues in zebrafish larvae. Depletion of MYDGF impairs wound healing, and this phenotype is rescued by depleting neutrophils. Live imaging and photoconversion reveal impaired neutrophil reverse migration and inflammation resolution in mydgf mutants. We found that persistent neutrophil inflammation in tissues of mydgf mutants was dependent on the HIF-1 alpha pathway. Taken together, our data suggest that MYDGF is a damage signal that regulates neutrophil interstitial motility and inflammation through a HIF-1 alpha pathway in response to tissue damage.

Automated summary

MYDGF, induced by tissue damage, regulates neutrophil motility to damaged tissues through the HIF-1α pathway. Depletion of MYDGF impairs wound healing and inflammation resolution, while persistent neutrophil inflammation in MYDGF mutants is dependent on HIF-1α pathway.