Glucose Metabolism in Immune Regulation: From Mechanisms to Therapeutic Opportunities.

Immune cell activation and differentiation are tightly coupled to metabolic reprogramming, with glucose availability and intracellular glycolytic flux serving as central determinants of immune cell fate and function. While increased glucose uptake and aerobic glycolysis support rapid proliferation and effector programs, persistent glucose abundance or dysregulated glycolytic signaling can contribute to immune dysfunction, chronic inflammation, and impaired host defense. Conversely, controlled limitation of glucose availability-through altered systemic supply, tissue microenvironmental competition, or targeted modulation of glycolysis-can rebalance immune metabolism toward oxidative phosphorylation, fatty acid oxidation, and mitochondrial fitness. This review examines how glucose availability and glycolytic flux operate as metabolic checkpoints that integrate with nutrient-sensing pathways, including mTORC1, AMPK, and HIF-1α, to shape immune activation, effector differentiation, and memory formation. We discuss evidence across disease contexts, including hyperglycemia-associated immune dysfunction, viral infection, autoimmunity, and cancer, and summarize emerging strategies to therapeutically modulate glucose metabolism using dietary interventions and pharmacologic tools. By distinguishing dietary carbohydrate intake from systemic glucose availability and cell-intrinsic glycolytic control, this review provides a coherent framework for understanding when glucose modulation can enhance immunity and when it risks immune suppression or metabolic exhaustion.