Glutamine metabolism tunes myeloid responses to drive resolution of inflammation during skin repair

Tissue repair requires inflammation resolution, but the molecular mechanisms involved in vivo are not fully understood. Here, we show that glutamine metabolism suppresses neutrophil recruitment to abrogate inflammation and drive skin wound repair. Integrated metabolomic and transcriptional profiling identified glutamine metabolism as enriched in macrophages during resolution. Dietary depletion studies and conditional deletion of glutaminase, the enzyme essential for glutamine metabolism, in mouse myeloid cells revealed that macrophages suppress neutrophil recruitment genes during tissue resolution to promote repair. We also found that these genes are upregulated in macrophages in patients with diabetes. Mechanistically, our data reveal that glutamine metabolism in macrophages induces suppressive chromatin remodeling of neutrophil recruitment genes, including Ccl ligands, during resolution of inflammation. These findings highlight the ability of specific metabolites to control cellular communication during tissue repair, with glutamine specifically to suppress neutrophil recruitment to advance inflammation resolution.