Rewiring immunity in rheumatoid arthritis: metabolic and epigenetic therapeutic strategies

Rheumatoid arthritis (RA) is a systemic autoimmune disease marked by chronic inflammation and destruction of joints and surrounding soft tissues. The pathogenesis of RA is heavily driven by two intertwined and mutually regulatory processes: metabolic reprogramming and epigenetic remodeling. Recent advances reveal a crucial crosstalk wherein metabolic intermediates derived from immune cells act as substrates or cofactors for chromatin-modifying enzymes. This interplay profoundly shapes epigenetic landscapes, thereby exacerbating inflammatory responses and disease progression. Here, we review the mechanisms underlying immune cell metabolic reprogramming in RA and critically examine how metabolite-mediated epigenetic remodeling orchestrates disease pathology. Furthermore, we summarize state-of-the-art epigenetic-targeted therapeutic strategies, offering new insights and a solid theoretical basis for treating RA through the metabolic-epigenetic axis.