α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming.

Détails

ID Serval
serval:BIB_CA3F4F3BEF1D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming.
Périodique
Nature immunology
Auteur(s)
Liu P.S., Wang H., Li X., Chao T., Teav T., Christen S., Di Conza G., Cheng W.C., Chou C.H., Vavakova M., Muret C., Debackere K., Mazzone M., Huang H.D., Fendt S.M., Ivanisevic J., Ho P.C.
ISSN
1529-2916 (Electronic)
ISSN-L
1529-2908
Statut éditorial
Publié
Date de publication
09/2017
Peer-reviewed
Oui
Volume
18
Numéro
9
Pages
985-994
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages. As such, αKG contributes to endotoxin tolerance after M1 activation. This study reveals new mechanistic regulations by which glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming.

Mots-clé
Animals, Cellular Reprogramming/immunology, Chromatin Immunoprecipitation, Citric Acid Cycle/immunology, Epigenesis, Genetic, Fatty Acids/metabolism, Gene Expression Profiling, Glutamine/metabolism, Glycolysis/immunology, Ketoglutaric Acids/immunology, Ketoglutaric Acids/metabolism, Lipopolysaccharides, Macrophage Activation/immunology, Macrophages/immunology, Macrophages/metabolism, Metabolomics, Mice, NF-kappa B/immunology, Oxidation-Reduction, Oxidative Phosphorylation, Phenotype, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA, Succinic Acid/metabolism
Pubmed
Web of science
Création de la notice
10/08/2017 14:02
Dernière modification de la notice
20/08/2019 16:45
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