| First Author | Zhang S | Year | 2019 |
| Journal | Cell Metab | Volume | 29 |
| Issue | 2 | Pages | 443-456.e5 |
| PubMed ID | 30595481 | Mgi Jnum | J:272044 |
| Mgi Id | MGI:6282533 | Doi | 10.1016/j.cmet.2018.12.004 |
| Citation | Zhang S, et al. (2019) Efferocytosis Fuels Requirements of Fatty Acid Oxidation and the Electron Transport Chain to Polarize Macrophages for Tissue Repair. Cell Metab 29(2):443-456.e5 |
| abstractText | During wound injury, efferocytosis fills the macrophage with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to how metabolic phagocytic signaling regulates the signature anti-inflammatory macrophage response. Here we report the metabolome of activated macrophages during efferocytosis to reveal an interleukin-10 (IL-10) cytokine escalation that was independent of glycolysis yet bolstered by apoptotic cell fatty acids and mitochondrial beta-oxidation, the electron transport chain, and heightened coenzyme NAD(+). Loss of IL-10 due to mitochondrial complex III defects was remarkably rescued by adding NAD(+) precursors. This activated a SIRTUIN1 signaling cascade, largely independent of ATP, that culminated in activation of IL-10 transcription factor PBX1. Il-10 activation by the respiratory chain was also important in vivo, as efferocyte mitochondrial dysfunction led to cardiac rupture after myocardial injury. These findings highlight a new paradigm whereby macrophages leverage efferocytic metabolites and electron transport for anti-inflammatory reprogramming that culminates in organ repair. |
