Abstract

Autoimmune diseases (ADs) are characterized by a breakdown of immune tolerance, leading to chronic inflammation and tissue damage. Emerging evidence suggests that metabolic reprogramming, particularly alterations in cellular glycolysis, plays a critical and often overlooked role in regulating immune cell function and driving AD pathogenesis. This review article investigates the growing relationship between enhanced glycolytic flux—the Warburg effect—and the activation, proliferation, and effector function of various immune cell subsets, including T cells, B cells, and macrophages, which are central to ADs. We synthesize findings from recent in vitro, in vivo, and clinical studies to elucidate the molecular mechanisms by which glycolytic enzymes and their intermediates act as signaling molecules to modulate gene expression and cytokine production. Key findings highlight that targeting specific glycolytic checkpoints, such as PFKFB3 or lactate dehydrogenase, can selectively suppress pathogenic immune responses while preserving regulatory functions. The significance of this work lies in establishing glycolysis as a promising therapeutic target for ADs, moving beyond traditional immunosuppression to a strategy that addresses the underlying metabolic dysregulation of the immune system. Further research is warranted to translate these findings into novel, effective clinical interventions.