Immunometabolism: an overview and therapeutic prospects in autoimmune diseases

Abstract

Metabolism is a critical immune regulator under physiologic and pathologic conditions. Culminating evidence has disentangled the contribution of distinct metabolic pathways, namely glucolysis, pentose phosphate, fatty acid oxidation, glutaminolysis, Krebs cycle and oxidative phosphorylation, in modulating innate and adaptive immune cells based on their activation/differentiation state. Metabolic aberrations and changes in the intracellular levels of specific metabolites are linked to the inflammatory phenotype of immune cells implicated in autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and diabetes. Notably, targeting metabolism such as the mTOR by rapamycin, hexokinase by 2-deoxy-D-glucose, AMP-activated protein kinase by metformin, may be used to ameliorate autoimmune inflammation. Accordingly, research in immunometabolism is expected to offer novel opportunities for monitoring and treating immune-mediated diseases.

Keywords: adaptive immunity; autoimmune disease; biomarkers; glycolysis; innate immunity; metabolites; microbiota; oxidative phosphorylation.