Macrophages respond to various signals through different pathways and subsequently undergo a phenotypic switch that determines their role in inflammation. In addition to enhancing TLR signaling of macrophages by increasing absorption of LPS, we must consider the effects of increased mitochondrial stress induced by Notch-mediated glycolysis and OXPHOS. The article by Xu et al. clearly addresses a novel metabolic function of Notch in regulating M1 macrophage activation in response to TLR signaling and mitochondrial stress. Therefore, in addition to targeting the developmental regulatory role of Notch, new agents targeting Notch signaling should be developed, and their roles in human ASH should be determined. 

Hepatology. 2016 Apr;63(4):1381-3. doi: 10.1002/hep.28386. Review.