Гостевая лекция по системной иммунологии — Максим Артемов

Network integration of parallel metabolomic-transcriptional data reveals novel metabolic modules regulating divergent macrophage polarization.

Maxim Artyomov (PhD), Washington University in St. Louis

Macrophages polarize to divergent functional phenotypes in a highly coordinated process of metabolic and transcriptional rewiring that is still poorly understood. We developed an Integrated Metabolomics and Gene Expression (IMAGE) profiling and analysis pipeline and applied it to extensively characterize global metabolic programs of macrophage polarization. IMAGE analysis identified multiple novel modules responsible for metabolic rewiring during polarization, which we validated through extensive carbon and nitrogen labeling experiments. M1-specific modules included inflammatory variant of the aspartate-arginosuccinate shunt and TCA break-point at Idh accompanied by citrate accumulation diverted towards itaconate and fatty acid synthesis. In M2 macrophages we discovered significant role of glutamine, whereby it supports TCA cycle and provides nitrogen for UDP-GlcNAc synthesis. Consistently, glutamine deprivation resulted in a significant, M2-specific defect in polarization. Our data provide, for the first time, a global view of the integrated transcriptional and metabolic changes that result in M1 and M2 polarization.