| First Author | Zhang W | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 12 | Pages | 3180-3193 |
| PubMed ID | 30463876 | Mgi Jnum | J:269772 |
| Mgi Id | MGI:6272999 | Doi | 10.1084/jem.20181211 |
| Citation | Zhang W, et al. (2018) The E3 ligase VHL controls alveolar macrophage function via metabolic-epigenetic regulation. J Exp Med 215(12):3180-3193 |
| abstractText | Metabolic pathways such as glycolysis or oxidative phosphorylation play a key role in regulating macrophage function during inflammation and tissue repair. However, how exactly the VHL-HIF-glycolysis axis is involved in the function of tissue-resident macrophages remains unclear. Here we demonstrate that loss of VHL in myeloid cells resulted in attenuated pulmonary type 2 and fibrotic responses, accompanied by reduced eosinophil infiltration, decreased IL-5 and IL-13 concentrations, and ameliorated fiber deposition upon challenge. VHL deficiency uplifted glycolytic metabolism, decreased respiratory capacity, and reduced osteopontin expression in alveolar macrophages, which impaired the function of type 2 innate lymphoid cells but was significantly reversed by HIF1alpha inhibition or ablation. The up-regulated glycolysis altered the epigenetic modification of osteopontin gene, with the metabolic intermediate 3-phosphoglyceric acid as a key checkpoint controller. Thus, our results indicate that VHL acts as a crucial regulatory factor in lung inflammation and fibrosis by regulating alveolar macrophages. |
