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 RHEUMATOID ARTHRITIS IN 2018

Cell metabolism as a potentially targetable pathway in RA

Cell metabolism has long been at the forefront of tumour biology, but in the past decade the importance of cellular bioenergetics has been increasingly recognized in regulating immune cell function. Mechanistic studies in 2018 have highlighted cell metabolism as a potential therapeutic target for the treatment of rheumatoid arthritis.

Key advances

  • Fibroblast-like synoviocytes are hyper-glycolytic and express large amounts of hexokinase 2 (HK2), which mediates their invasive phenotype; the blockade of HK2 represents a novel therapeutic strategy1.

  • Succinate uptake via succinate receptor GPR91 induces an angiogenic phenotype in endothelial cells through hypoxia-inducible factor 1α-mediated vascular endothelial growth factor secretion, leading to increased migration, invasion and vessel sprouting2.

  • In rheumatoid arthritis and coronary artery disease, macrophages have increased metabolic activity, a process mediated by glycogen synthase kinase 3β that depends on endoplasmic-reticulum-to-mitochondria calcium transport3.

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Fig. 1: Regulation of inflammation through metabolism.

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Correspondence to Ursula Fearon.

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McGarry, T., Fearon, U. Cell metabolism as a potentially targetable pathway in RA. Nat Rev Rheumatol 15, 70–72 (2019). https://doi.org/10.1038/s41584-018-0148-8

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