2. Academic Validation
  3. Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages

Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages

  • Cell Rep. 2024 Sep 24;43(9):114741. doi: 10.1016/j.celrep.2024.114741.
Hung-Jen Chen 1,  Daniel C Sévin 2,  Guillermo R Griffith 1,  Johanna Vappiani 2,  Lee M Booty 3,  Cindy P A A van Roomen 1,  Johan Kuiper 4,  Jeroen den Dunnen 5,  Wouter J de Jonge 6,  Rab K Prinjha 7,  Palwinder K Mander 7,  Paola Grandi 2,  Beata S Wyspianska 7,  Menno P J de Winther 8
Affiliations

Affiliations

  • 1 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.
  • 2 Cellzome, GSK R&D, 69117 Heidelberg, Germany.
  • 3 Immunology Network, Immunology Research Unit, GSK, SG1 2NY Stevenage, UK.
  • 4 Division of BioTherapeutics, Leiden Academic Centre for Drug Research, 2333 CL Leiden, the Netherlands.
  • 5 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.
  • 6 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.
  • 7 Immunology Research Unit, GSK Medicines Research Centre, SG1 2NY Stevenage, UK.
  • 8 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.
PMID: 39276347 DOI: 10.1016/j.celrep.2024.114741
Abstract

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.

Keywords

CP: Immunology; CP: Metabolism; Fc receptor; IDO1; IL4I1; cholesterol; glycolysis; immunometabolism; interferon; macrophage; metabolomics; tryptophan metabolism.

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