Figure 2.

Regulation of ILC2 metabolism by IL-33. Both glycolysis and OXPHOS are activated in IL-33-activated ILC2s, and the glycolytic process allows the uptake and storage of external lipids to fuel the proliferation of ILC2s. Four important regulators—HIF-1α, STAT3, arginase-1, and PPARγ—have been implicated in IL-33-activated ILC2s. HIF-1α drives the expression of the glycolytic enzyme PKM2 and the glycolytic metabolite pyruvate, which reduce H3K4me3 levels at ILC2-specific genes. IL-33 drives the activation of STAT3 and subsequent generation of SAM, which leads to increased H3K4me3 levels. IL-33 also increases the expression of PPARγ, which mediates lipid metabolism in ILC2s. The enzyme arginase-1 promotes the generation of l-arginine-derived polyamines and is closely related to aerobic glycolysis in IL-33-activated ILC2s. OXPHOS, oxidative phosphorylation; PKM2, pyruvate kinase M2; SAM, S-adenosylmethionine.