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Interleukin-17 as a key player in neuroimmunometabolism

Nature Metabolism volume 5, pages 1088–1100 (2023)Cite this article

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Abstract

In mammals, interleukin (IL)-17 cytokines are produced by innate and adaptive lymphocytes. However, the IL-17 family has widespread expression throughout evolution, dating as far back as cnidaria, molluscs and worms, which predate lymphocytes. The evolutionary conservation of IL-17 suggests that it is involved in innate defence strategies, but also that this cytokine family has a fundamental role beyond typical host defence. Throughout evolution, IL-17 seems to have a major function in homeostatic maintenance at barrier sites. Most recently, a pivotal role has been identified for IL-17 in regulating cellular metabolism, neuroimmunology and tissue physiology, particularly in adipose tissue. Here we review the emerging role of IL-17 signalling in regulating metabolic processes, which may shine a light on the evolutionary role of IL-17 beyond typical immune responses. We propose that IL-17 helps to coordinate the cross-talk among the nervous, endocrine and immune systems for whole-body energy homeostasis as a key player in neuroimmunometabolism.

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Fig. 1: Timeline of major neuroimmunometabolic discoveries involving IL-17.
Fig. 2: IL-17-mediated signalling in target cells.
Fig. 3: Structural relationships between IL-17A, IL-17F and an archetypal neurotrophic factor.
Fig. 4: IL-17 signalling modulates cellular metabolism in a host of non-immune target cells.
Fig. 5: Evidence for evolutionarily conserved roles for IL-17 signalling beyond immunity.

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Acknowledgements

The authors are supported by the NIH (5R01AI134861), Science Foundation Ireland (16/FRL/3865) and an Irish Research Council (IRC) Fellowship (A.D.).

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  1. School of Biochemistry and Immunology, TBSI, Trinity College Dublin, Dublin, Ireland

    Aaron Douglas, Brenneth Stevens & Lydia Lynch

  2. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Brenneth Stevens & Lydia Lynch

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A.D. and B.S. drafted the figures, and L.L. revised the final version of the figures. A.D., B.S. and L.L. jointly conceived, wrote and revised the final version of the manuscript.

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Douglas, A., Stevens, B. & Lynch, L. Interleukin-17 as a key player in neuroimmunometabolism. Nat Metab 5, 1088–1100 (2023). https://doi.org/10.1038/s42255-023-00846-3

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