Type 2 Inflammatory Diseases: The Crossroads of Immunity and Metabolism

The understanding of type 2 inflammatory diseases is undergoing a paradigm shift from "immune imbalance" toward "immune-metabolic crosstalk". Energy metabolism not only fuels immune responses but also fundamentally dictates the functional phenotypes of immune cells through metabolic reprogramming. By systematically integrating metabolic programming data of key immune cells across diverse tissues (skin, gut, nasal, and ocular mucosa), this review constructs a cross-disease "metabolism-signaling network" atlas. The synthesis highlights that glycolysis and mTORC1 signaling are predominantly coupled with the pro-inflammatory outputs of Th2 cells and ILC2s, whereas fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) sustain the homeostasis of Tregs and M2-like macrophages. Furthermore, this review characterizes how the tryptophan, glutamine, and arginine pathways fine-tune the immune tolerance boundary via the IDO-AhR-mTOR axis. We also elucidate a conserved inter-organ "hypoxia-HIF-1α-lactylation" axis, which, in conjunction with tissue-specific metabolic branches (e.g., the ceramide pathway in the skin, the SCFA circuit in the gut, and the lactate-GPR81 loop in the mucosa), collectively sculpts local microenvironments and remodeling trajectories. Ultimately, a novel diagnostic and therapeutic framework centered on metabolic phenotyping is proposed, providing prospective insights into targeting metabolic checkpoints for precision immunotherapy in type 2 inflammation.