Fine tuning of immunometabolism for the treatment of rheumatic diseases

Abstract

All immune cells depend on specific and efficient metabolic pathways to mount an appropriate response. Over the past decade, the field of immunometabolism has expanded our understanding of the various means by which cells modulate metabolism to achieve the effector functions necessary to fight infection or maintain homeostasis. Harnessing these metabolic pathways to manipulate inappropriate immune responses as a therapeutic strategy in cancer and autoimmunity has received increasing scrutiny by the scientific community. Fine tuning immunometabolism to provide the desired response, or prevent a deleterious response, is an attractive alternative to chemotherapy or overt immunosuppression. The various metabolic pathways used by immune cells in rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis offer numerous opportunities for selective targeting of specific immune cell subsets to manipulate cellular metabolism for therapeutic benefit in these rheumatologic diseases.

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Figure 1: Metabolic reprogramming of immune cell populations matches immunological function.
Figure 2: Metabolic processes to target in the treatment of rheumatologic diseases.

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Acknowledgements

The authors would like to thank members of the Rathmell and Major labs for their contributions and intellectual input. The authors' work is supported by the Alliance for Lupus Research (J.C.R.), NIH National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK105550 (J.C.R.), the Lupus Research Alliance (A.S.M.), U.S. Department of Veterans Affairs Merit Award I0BX002968 (A.S.M.) and NIH National Heart, Lung, and Blood Institute grant F31 HL128040 (J.P.R.).

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All authors researched the data for the article, provided a substantial contribution to discussions of the content and contributed to writing the article and to review and/or editing of the manuscript before submission.

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Correspondence to Jeffrey C. Rathmell.

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Rhoads, J., Major, A. & Rathmell, J. Fine tuning of immunometabolism for the treatment of rheumatic diseases. Nat Rev Rheumatol 13, 313–320 (2017). https://doi.org/10.1038/nrrheum.2017.54

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