Amino acid metabolic reprogramming is an important component of immunometabolism. In addition to providing biosynthetic substrates and energetic support for macrophages, distinct amino acid metabolic pathways can also reshape the inflammatory and reparative functional states of macrophages by regulating redox homeostasis, epigenetic modifications, signal transduction, and the accumulation of metabolic intermediates. Despite rapid progress in this field, there remains a lack of systematic integration regarding how key metabolic axes, including arginine metabolism, tryptophan catabolism, and glutamine metabolism, coordinately or antagonistically drive macrophage functional reprogramming, as well as the conservation, heterogeneity, and translational significance of these changes across different autoimmune-related diseases. This review summarizes the roles of arginine, tryptophan, glutamine, branched-chain amino acid, serine/glycine/threonine, aspartate/asparagine, and sulfur-containing amino acid metabolism in the dynamic spectrum of macrophage polarization, and further outlines recent advances in systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes mellitus, psoriasis, autoimmune hepatitis, and vasculitis. This review emphasizes that amino acid metabolism is not an isolated regulatory module, but rather part of an interconnected network that, together with glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle anaplerosis, one-carbon metabolism, and lipid metabolism, determines macrophage fate. Given the existing differences in evidence strength and metabolic phenotypes among in vitro systems, animal models, and human studies, caution is still required when extrapolating these conclusions to clinical settings. Overall, therapeutic interventions targeting amino acid metabolism may provide novel biomarkers and treatment strategies for autoimmune-related diseases, but their clinical translation still depends on higher-resolution human validation and mechanism-oriented precision studies.
Yin et al. (Thu,) studied this question.