Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages.

Autor:	Chen HJ; Department of Medical Biochemistry, Experimental Vascular Biology, Atherosclerosis and Ischemic Syndromes, Amsterdam Cardiovascular Sciences, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., Sévin DC; Cellzome, GSK R&D, 69117 Heidelberg, Germany., Griffith GR; Department of Medical Biochemistry, Experimental Vascular Biology, Atherosclerosis and Ischemic Syndromes, Amsterdam Cardiovascular Sciences, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., Vappiani J; Cellzome, GSK R&D, 69117 Heidelberg, Germany., Booty LM; Immunology Network, Immunology Research Unit, GSK, SG1 2NY Stevenage, UK., van Roomen CPAA; Department of Medical Biochemistry, Experimental Vascular Biology, Atherosclerosis and Ischemic Syndromes, Amsterdam Cardiovascular Sciences, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., Kuiper J; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, 2333 CL Leiden, the Netherlands., Dunnen JD; Center for Experimental and Molecular Medicine, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., de Jonge WJ; Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 BK Amsterdam, the Netherlands., Prinjha RK; Immunology Research Unit, GSK Medicines Research Centre, SG1 2NY Stevenage, UK., Mander PK; Immunology Research Unit, GSK Medicines Research Centre, SG1 2NY Stevenage, UK., Grandi P; Cellzome, GSK R&D, 69117 Heidelberg, Germany., Wyspianska BS; Immunology Research Unit, GSK Medicines Research Centre, SG1 2NY Stevenage, UK., de Winther MPJ; Department of Medical Biochemistry, Experimental Vascular Biology, Atherosclerosis and Ischemic Syndromes, Amsterdam Cardiovascular Sciences, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. Electronic address: m.dewinther@amsterdamumc.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Sep 24; Vol. 43 (9), pp. 114741. Date of Electronic Publication: 2024 Sep 13.
DOI:	10.1016/j.celrep.2024.114741
Abstrakt:	Macrophages exhibit diverse phenotypes and respond flexibly to environmental cues through metabolic remodeling. In this study, we present a comprehensive multi-omics dataset integrating intra- and extracellular metabolomes with transcriptomic data to investigate the metabolic impact on human macrophage function. Our analysis establishes a metabolite-gene correlation network that characterizes macrophage activation. We find that the concurrent inhibition of tryptophan catabolism by IDO1 and IL4I1 inhibitors suppresses the macrophage pro-inflammatory response, whereas single inhibition leads to pro-inflammatory activation. We find that a subset of anti-inflammatory macrophages activated by Fc receptor signaling promotes glycolysis, challenging the conventional concept of reduced glycolysis preference in anti-inflammatory macrophages. We demonstrate that cholesterol accumulation suppresses macrophage IFN-γ responses. Our integrated network enables the discovery of immunometabolic features, provides insights into macrophage functional metabolic reprogramming, and offers valuable resources for researchers exploring macrophage immunometabolic characteristics and potential therapeutic targets for immune-related disorders. Competing Interests: Declaration of interests GSK provided support in the form of salary for L.M.B., J.V., P.G., B.S.W., R.K.P., P.K.M., and D.C.S. GSK had no additional role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. Funding for the open-access charges is covered by Amsterdam University Medical Centers, University of Amsterdam. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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