| First Author | Dang B | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 5 | Pages | 112471 |
| PubMed ID | 37149865 | Mgi Jnum | J:348574 |
| Mgi Id | MGI:7491446 | Doi | 10.1016/j.celrep.2023.112471 |
| Citation | Dang B, et al. (2023) The glycolysis/HIF-1alpha axis defines the inflammatory role of IL-4-primed macrophages. Cell Rep 42(5):112471 |
| abstractText | 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(INF)) macrophages occurs after the IL-4Ralpha/Stat6 axis. Glycolysis supports Hif-1alpha stabilization and proinflammatory phenotype of M2(INF) macrophages. Inhibiting glycolysis blunts Hif-1alpha accumulation and M2(INF) phenotype. Wdr5-dependent H3K4me3 mediates the long-lasting effect of IL-4, with Wdr5 knockdown inhibiting M2(INF) macrophages. Our results also show that the induction of M2(INF) macrophages by IL-4 intraperitoneal injection and transferring of M2(INF) macrophages confer a survival advantage against bacterial infection in vivo. In conclusion, our findings highlight the previously neglected non-canonical role of M2(INF) 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. |
