Immunometabolism: Linking Cellular Energy Pathways with Immune Responses in Health and Disease

Abstract

Immunometabolism, the interdisciplinary nexus between cellular metabolism and immune regulation, has emerged as a pivotal field in understanding how metabolic cues shape immune cell fate, function, and pathogenicity. Beyond merely supporting energy demands, metabolic pathways actively reprogram immune cells by modulating signaling cascades, transcriptional networks, and epigenetic landscapes. During immune activation, immune cells dynamically transition between metabolic states, such as glycolysis, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, to meet distinct functional requirements. Dysregulation of these pathways has been implicated in chronic inflammation, autoimmune disorders, cancer progression, metabolic syndromes, and infectious diseases. Recent advances in single-cell technologies, metabolomics, and imaging have expanded our understanding of how nutrient availability and metabolic checkpoints govern immunity. Moreover, therapeutic targeting of immunometabolic pathways, ranging from glycolytic inhibition to mitochondrial bioenergetic enhancement, offers promising interventions for diverse clinical conditions, including cancer immunotherapy and metabolic inflammatory diseases. This review consolidates current insights into the metabolic regulation of innate and adaptive immune responses, emphasizing physiological homeostasis and pathological alterations, while also exploring emerging translational opportunities in immunometabolic therapeutics.