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IL-17 receptor–based signaling and implications for disease

Nature Immunology volume 20, pages 1594–1602 (2019)Cite this article

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Abstract

IL-17 is a highly versatile pro-inflammatory cytokine crucial for a variety of processes, including host defense, tissue repair, the pathogenesis of inflammatory disease and the progression of cancer. In contrast to its profound impact in vivo, IL-17 exhibits surprisingly moderate activity in cell-culture models, which presents a major knowledge gap about the molecular mechanisms of IL-17 signaling. Emerging studies are revealing a new dimension of complexity in the IL-17 pathway that may help explain its potent and diverse in vivo functions. Discoveries of new mRNA stabilizers and receptor-directed mRNA metabolism have provided insights into the means by which IL-17 cooperates functionally with other stimuli in driving inflammation, whether beneficial or destructive. The integration of IL-17 with growth-receptor signaling in specific cell types offers new understanding of the mitogenic effect of IL-17 on tissue repair and cancer. This Review summarizes new developments in IL-17 signaling and their pathophysiological implications.

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Fig. 1: Overview of IL-17 signaling functions in vivo.
Fig. 2: Canonical IL-17 signaling pathways.
Fig. 3: Noncanonical IL-17 signaling.

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Acknowledgements

Supported by US National Institutes of Health grants DE022550 and AI107825 (S.L.G.), P01CA062220 and P01HL103453 (X.L.) and R01AI110822-01 (M.J.M.), and by the National Multiple Sclerosis Society grant RG5130A2/1 (X.L.).

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Authors and Affiliations

  1. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Xiaoxia Li & Junjie Zhao

  2. University of Pittsburgh, Division of Rheumatology & Clinical Immunology, Pittsburgh, PA, USA

    Rami Bechara, Mandy J. McGeachy & Sarah L. Gaffen

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  1. Xiaoxia Li
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Correspondence to Xiaoxia Li or Sarah L. Gaffen.

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Li, X., Bechara, R., Zhao, J. et al. IL-17 receptor–based signaling and implications for disease. Nat Immunol 20, 1594–1602 (2019). https://doi.org/10.1038/s41590-019-0514-y

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