The immunologic Warburg effect: Evidence and therapeutic opportunities in autoimmunity. (27th February 2020)

• Record Type: Journal Article
• Authors: Kornberg, Michael D.
• Is Part Of: Wiley interdisciplinary reviews. Volume 12:Number 5(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-27
• Subjects: aerobic glycolysis -- autoimmune disease -- immunology -- immunometabolism -- Warburg effect; Systems biology -- Periodicals; Medicine -- Periodicals; 610
• DOI: 10.1002/wsbm.1486
• Languages: English
• ISSNs: 1939-5094

Abstract

Abstract: Pro‐inflammatory signals induce metabolic reprogramming in innate and adaptive immune cells of both myeloid and lymphoid lineage, characterized by a shift to aerobic glycolysis akin to the Warburg effect first described in cancer. Blocking the switch to aerobic glycolysis impairs the survival, differentiation, and effector functions of pro‐inflammatory cell types while favoring anti‐inflammatory and regulatory phenotypes. Glycolytic reprogramming may therefore represent a selective vulnerability of inflammatory immune cells, providing an opportunity to modulate immune responses in autoimmune disease without broad toxicity in other tissues of the body. The mechanisms by which aerobic glycolysis and the balance between glycolysis and oxidative phosphorylation regulate immune responses have only begun to be understood, with many additional insights expected in the years to come. Immunometabolic therapies targeting aerobic glycolysis include both pharmacologic inhibitors of key enzymes and glucose‐restricted diets, such as the ketogenic diet. Animal studies support a role for these pharmacologic and dietary therapies for the treatment of autoimmune diseases, and in a few cases proof of concept has been demonstrated in human disease. Nonetheless, much more work is needed to establish the clinical safety and efficacy of these treatments. This article is categorized under: Biological Mechanisms > Metabolism Translational, Genomic, and Systems Medicine > Translational Medicine Biological Mechanisms > Cell Signaling Abstract : The immunologic Warburg effect represents a potential target for treating autoimmune diseases, through both pharmacologic and dietary strategies. The mechanisms explaining the requirement for aerobic glycolysis in immune activation remain only partially understood.