The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages.

Détails

ID Serval
serval:BIB_2E097BAB796F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages.
Périodique
Cell reports
Auteur⸱e⸱s
Dang B., Gao Q., Zhang L., Zhang J., Cai H., Zhu Y., Zhong Q., Liu J., Niu Y., Mao K., Xiao N., Liu W.H., Lin S.H., Huang J., Huang S.C., Ho P.C., Cheng S.C.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
30/05/2023
Peer-reviewed
Oui
Volume
42
Numéro
5
Pages
112471
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
T helper type 2 (Th2) cytokine-activated M2 macrophages contribute to inflammation resolution and wound healing. This study shows that IL-4-primed macrophages exhibit a stronger response to lipopolysaccharide stimulation while maintaining M2 signature gene expression. Metabolic divergence between canonical M2 and non-canonical proinflammatory-prone M2 (M2 <sub>INF</sub> ) macrophages occurs after the IL-4Rα/Stat6 axis. Glycolysis supports Hif-1α stabilization and proinflammatory phenotype of M2 <sub>INF</sub> macrophages. Inhibiting glycolysis blunts Hif-1α accumulation and M2 <sub>INF</sub> phenotype. Wdr5-dependent H3K4me3 mediates the long-lasting effect of IL-4, with Wdr5 knockdown inhibiting M2 <sub>INF</sub> macrophages. Our results also show that the induction of M2 <sub>INF</sub> macrophages by IL-4 intraperitoneal injection and transferring of M2 <sub>INF</sub> macrophages confer a survival advantage against bacterial infection in vivo. In conclusion, our findings highlight the previously neglected non-canonical role of M2 <sub>INF</sub> macrophages and broaden our understanding of IL-4-mediated physiological changes. These results have immediate implications for how Th2-skewed infections could redirect disease progression in response to pathogen infection.
Mots-clé
Humans, Interleukin-4/pharmacology, Interleukin-4/metabolism, Macrophages/metabolism, Inflammation/metabolism, Cytokines/metabolism, Glycolysis/physiology, Hypoxia-Inducible Factor 1, alpha Subunit/metabolism, Intracellular Signaling Peptides and Proteins/metabolism, CP: Immunology, CP: Metabolism, Hif1α, IL-4, M2 macrophage, epigenetics, glycolysis, trained immunity
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/05/2023 13:47
Dernière modification de la notice
13/10/2023 7:01
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