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• W4309221118 abstract "Abstract T helper type 2 (Th2) cytokine-activated M2 macrophages play a major role in inflammation resolution and wound healing. Myriads of studies have demonstrated the anti-inflammatory feature of M2 macrophages. In the present study, we report that IL-4-primed macrophages respond more robustly to the subsequent LPS stimulation despite maintaining the canonical M2 signature gene expression. The canonical M2 and non-canonical proinflammatory-prone macrophages (M2 INF ) diverge metabolically after the common IL-4Ra/Stat6 axis. While the Gln/α-KG/Jmjd3 axis is indispensable for M2 differentiation, the glycolysis/Hif-1α axis is critical for IL-4-induced M2 INF . The elevated glycolysis sustains Hif-1αstabilization and the pro-inflammatory phenotype of M2 INF . Conversely, inhibition of glycolysis blunts Hif-1αaccumulation and M2 INF . Macrophages from myeloid-specific Hif-1α KO mice retain M2 differentiation capacity but fail to induce M2 INF . Wdr5-dependent H3K4me3 epigenetic modification mediates the long-lasting effect of IL-4 as the knocking down of Wdr5 inhibits M2 INF . Moreover, the induction of M2 INF by IL-4 intraperitoneal injection and transferring of M2 INF provides a survival advantage against bacterial infection in vivo . To conclude, our findings delineate the previously neglected non-canonical role of M2 INF. This will broaden our understanding of IL-4-mediated physiological changes and provide immediate impacts on how Th2-skewed infections could re-direct disease progression in response to pathogen infection." @default.
• W4309221118 created "2022-11-24" @default.
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• W4309221118 date "2022-11-16" @default.
• W4309221118 modified "2023-10-16" @default.
• W4309221118 title "The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed 2 macrophages" @default.
• W4309221118 doi "https://doi.org/10.21203/rs.3.rs-1322480/v2" @default.
• W4309221118 hasPublicationYear "2022" @default.
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