| First Author | Liu PS | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 9 | Pages | 985-994 |
| PubMed ID | 28714978 | Mgi Jnum | J:258709 |
| Mgi Id | MGI:6140417 | Doi | 10.1038/ni.3796 |
| Citation | Liu PS, et al. (2017) alpha-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol 18(9):985-994 |
| abstractText | Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of alpha-ketoglutarate (alphaKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high alphaKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages. As such, alphaKG contributes to endotoxin tolerance after M1 activation. This study reveals new mechanistic regulations by which glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming. |
