Immunometabolic shifts in autoimmune disease: Mechanisms and pathophysiological implications

Autoimmune diseases occur when the immune system abnormally attacks the body's normal tissues, causing inflammation and damage. Each disease has unique immune and metabolic dysfunctions during pathogenesis. In rheumatoid arthritis (RA), immune cells have different metabolic patterns and mitochondrial/lysosomal dysfunctions at different disease stages. In systemic lupus erythematosus (SLE), type I interferon (IFN) causes immune cell metabolic dysregulation, linking activation to metabolic shifts that may worsen the disease. In systemic sclerosis (SSc), mitochondrial changes affect fibroblast metabolism and the immune response. Idiopathic inflammatory myopathies (IIMs) patients have mitochondrial and metabolic issues. In primary Sjögren's syndrome (pSS), immune cell metabolism is imbalanced and mitochondrial damage can lead to cell/tissue damage. Metabolic reprogramming links cellular energy needs and immune dysfunctions, causing inflammation, damage, and symptoms in these diseases. It also affects immune cell functions like differentiation, proliferation, and secretion. This review discusses the potential of targeting metabolic pathways to restore immune balance, offering directions for future autoimmune disease research and treatment.