Immunometabolism in health and disease: from cellular metabolic reprogramming to therapeutic opportunities

Abstract

Cellular metabolism actively shapes immune cell fate, function, and lineage commitment through coordinated metabolic reprogramming, rather than serving merely as a passive energy supply. Distinct metabolic pathways, including glycolysis, mitochondrial respiration, fatty acid oxidation, and amino acid catabolism, govern the functional polarization of innate and adaptive immune cells. Accordingly, immunometabolic dysregulation contributes to the pathogenesis of diverse human diseases, including cancer, metabolic disorders, autoimmune disorders, and infectious diseases. Targeting central nutrient-sensing pathways involving mechanistic target of rapamycin, adenosine monophosphate-activated protein kinase, hypoxia-inducible factor-1 alpha, and c-Myc may provide therapeutic avenues for restoring immune homeostasis. In parallel, single-cell multiomics, spatial metabolomics, and artificial intelligence-driven computational tools are defining immunometabolic heterogeneity with high resolution. This review summarizes the core principles of immunometabolism, describes cell-specific metabolic signatures, examines their roles in human disease, and outlines current therapeutic strategies and future directions for precision immunomodulation.