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Intertwining roles of circadian and metabolic regulation of the innate immune response

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Abstract

It has emerged that an interconnected relationship exists between metabolism, circadian rhythms, and the immune system. The relationship between metabolism and circadian rhythms is not that surprising given the necessity to align rhythms of feeding/fasting with activity/rest. Recently, our understanding of the importance of metabolic pathways in terms of immune function, termed immunometabolism, has grown exponentially. It is now appreciated that the time of day during which the innate immune system is challenged strongly conditions the subsequent response. Recent observations have found that many individual components that make up the circadian clock also control aspects of metabolism in innate immune cells to modulate inflammation. This circadian/metabolic axis may be a key factor driving rhythmicity of immune function and circadian disruption is associated with a range of chronic inflammatory diseases such as atherosclerosis, obesity, and diabetes. The field of “circadian immunometabolism” seeks to reveal undiscovered circadian controlled metabolic pathways that in turn regulate immune responses. The innate immune system has been intricately linked to chronic inflammatory diseases, and within the immune system, individual cell types carry out unique roles in inflammation. Therefore, circadian immunometabolism effects are unique to each innate immune cell.

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Funding

This work was funded by a Science Foundation Ireland Career Development Award (17/CDA/4688) and an Irish Research Council Laureate Award (IRCLA/2017/110) provided to A.M.C.

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Authors and Affiliations

  1. Curtis Clock Laboratory, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland

    Shannon L. Cox, James R. O’Siorain, Lauren E. Fagan, Annie M. Curtis & Richard G. Carroll

  2. Tissue Engineering Research Group (TERG), RCSI University of Medicine and Health Sciences, Dublin, Ireland

    Shannon L. Cox, James R. O’Siorain, Lauren E. Fagan, Annie M. Curtis & Richard G. Carroll

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Correspondence to Shannon L. Cox or Richard G. Carroll.

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This article is a contribution to the special issue on: Chronoimmunology: from preclinical assessments to clinical applications - Guest Editors: Henrik Oster & David Ray

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Annie M. Curtis and Richard G. Carroll are equal contributors.

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Cox, S.L., O’Siorain, J.R., Fagan, L.E. et al. Intertwining roles of circadian and metabolic regulation of the innate immune response. Semin Immunopathol 44, 225–237 (2022). https://doi.org/10.1007/s00281-021-00905-5

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