Exploring the metabolic mysteries: Mechanistic insights into lactylation-mediated regulation of autoimmune diseases.

Autoimmune diseases are chronic disorders caused by the immune system's aberrant recognition and attack of self-tissues. Accumulating evidence has revealed that these diseases are closely related to metabolic reprogramming and epigenetic regulation. Lactylation, a recently identified post-translational modification driven by lactate, has emerged as a critical link connecting cellular metabolism to immune regulation. In this review, we provide a comprehensive overview of the regulatory mechanisms and functional roles of lactylation in autoimmune pathogenesis. Lactate, by regulating both histone and non-histone lactylation, affects immune responses in both innate immunity (e.g., macrophages and dendritic cells) and adaptive immunity (e.g., T cells and B cells). The article focuses on exploring the specific regulatory mechanisms of lactate metabolism and lactylation in various autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and Sjögren's syndrome (SS). We describe how lactylation drives disease initiation and progression by modulating inflammatory responses, immune cell infiltration, and tissue damage, offering fresh perspectives on the pathophysiology of autoimmunity. Furthermore, lactylation-associated genes and modification levels demonstrate potential as disease biomarkers, suggesting that targeting lactate metabolic pathways or the involved enzymes can provide new therapeutic strategies and targets for autoimmune diseases.