The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages.
Details
Serval ID
serval:BIB_2E097BAB796F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages.
Journal
Cell reports
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
30/05/2023
Peer-reviewed
Oui
Volume
42
Number
5
Pages
112471
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
15/05/2023 12:47
Last modification date
13/10/2023 6:01