Figure 1.

IL-33 controls metabolic checkpoints in immune cells. There are several metabolic checkpoints by which IL-33 can participate in cellular metabolism. IL-33 activates the metabolic regulators mTORC1, PI3K-AKT, and AMPK, which coordinately influence downstream effector molecules, such as HIF-1α, Myc, and PPARγ, and subsequently orchestrate glycolytic and lipogenic programs. In this process, AMPK suppresses IL-33-induced NF-κB activation; intracellular IL-33 can also bind to NF-κB p65 and restricts its transcriptional activity, suggesting that a feedback loop controls cellular metabolic homeostasis. Additionally, IL-33 activates mitochondrial STAT3 via MAPK and fuels the methionine cycle.