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
Author(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)
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
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
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