@article{8c4491e58da941d3a28e7f4480557a88,
title = "Efferocytosis Fuels Requirements of Fatty Acid Oxidation and the Electron Transport Chain to Polarize Macrophages for Tissue Repair",
abstract = " 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 β-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. ",
keywords = "efferocytosis, immunometabolism, macrophage, wound healing",
author = "Shuang Zhang and Samuel Weinberg and Matthew DeBerge and Anastasiia Gainullina and Matthew Schipma and Kinchen, {Jason M.} and Issam Ben-Sahra and Gius, {David R.} and Laurent Yvan-Charvet and Chandel, {Navdeep S.} and Schumacker, {Paul T.} and Thorp, {Edward B.}",
note = "Funding Information: Funding support from NHLBI F32HL127958 (M.D.) and HL122309 and HL139812 (E.B.T.), Chicago Biomedical Consortium, AHA predoctoral fellowship to S.Z., NU presidential fellowship to S.Z., and Sidney Bess Memorial Fund. Special thanks to Lennell Reynolds, Jr. at the NU imaging facility. D.R.G. is supported by 2R01CA152601-A1, 1R01CA152799-01A1, 1R01CA168292-01A1, 1R01CA214025-01, the Avon Foundation for Breast Cancer Research, the Lynn Sage Cancer Research Foundation, the Zell Family Foundation, and the Chicago Biomedical Consortium as well the Searle Funds at The Chicago Community Trust. Funding Information: Funding support from NHLBI F32HL127958 (M.D.) and HL122309 and HL139812 (E.B.T.), Chicago Biomedical Consortium , AHA predoctoral fellowship to S.Z., NU presidential fellowship to S.Z., and Sidney Bess Memorial Fund . Special thanks to Lennell Reynolds, Jr. at the NU imaging facility. D.R.G. is supported by 2R01CA152601-A1 , 1R01CA152799-01A1 , 1R01CA168292-01A1 , 1R01CA214025-01 , the Avon Foundation for Breast Cancer Research, the Lynn Sage Cancer Research Foundation , the Zell Family Foundation, and the Chicago Biomedical Consortium as well the Searle Funds at The Chicago Community Trust . Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = feb,
day = "5",
doi = "10.1016/j.cmet.2018.12.004",
language = "English (US)",
volume = "29",
pages = "443--456.e5",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",
}