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  • Review Article
  • Published:

IL-17 in the immunopathogenesis of spondyloarthritis

Nature Reviews Rheumatology volume 14, pages 453–466 (2018)Cite this article

Subjects

Abstract

Spondyloarthritis (SpA) is a term that refers to a group of inflammatory diseases that includes psoriatic arthritis, axial SpA and nonradiographic axial SpA, reactive arthritis, enteropathic arthritis and undifferentiated SpA. The disease subtypes share clinical and immunological features, including joint inflammation (peripheral and axial skeleton); skin, gut and eye manifestations; and the absence of diagnostic autoantibodies (seronegative). The diseases also share genetic factors. The aetiology of SpA is still the subject of research by many groups worldwide. Evidence from genetic, experimental and clinical studies has accumulated to indicate a clear role for the IL-17 pathway in the pathogenesis of SpA. The IL-17 family consists of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F, of which IL-17A is the best studied. IL-17A is a pro-inflammatory cytokine that also has the capacity to promote angiogenesis and osteoclastogenesis. Of the six family members, IL-17A has the strongest homology with IL-17F. In this Review, we discuss how IL-17A and IL-17F and their cellular sources might contribute to the immunopathology of SpA.

Key points

  • Genetic and animal model studies indicate that the IL-23–IL-17 axis is involved in the pathogenesis of spondyloarthritis (SpA).

  • IL-17A has been identified directly in the blood and synovial fluid of patients with SpA, with T cells representing a key source of this cytokine.

  • IL-17A and IL-17F act in synergy with other pro-inflammatory mediators to induce pro-inflammatory responses across a range of cell types.

  • IL-23–IL-17-targeted therapies have been shown to be effective in psoriatic arthritis and ankylosing spondylitis.

  • Increased understanding of the pathogenic role of the IL-23–IL-17 axis, the cellular sources of these cytokines and their molecular regulation in SpA is essential to develop novel therapeutic strategies that target this pathway.

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Fig. 1: Key discoveries in the biology of IL-17A and IL-17-producing T cells.
Fig. 2: Hypothetical depiction of how spondyloarthritis susceptibility genes might influence IL-23–IL-17-mediated immune responses.
Fig. 3: Potential synergistic activity of IL-17A and TNF in the spondyloarthritis joint.

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Acknowledgements

The authors acknowledge support from the King’s Health Partners Research and Development challenge fund (R140808) (to L.S.T., B.W.K and K.J.A.S), a King’s Health Schools PhD studentship funded by a Medical Research Council doctoral training grant (to L.S.T. and U.S.), a Biotechnology and Biological Sciences Research Council (BBSRC) Collaborative Awards in Science and Engineering (CASE) PhD studentship (BB/M503289/1) (to L.S.T. and L.A.B.) and support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London (to L.S.T., B.W.K. and K.J.A.S.). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health.

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Nature Reviews Rheumatology thanks P. Bowness, F. van Wijk and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Centre for Inflammation Biology and Cancer Immunology (CIBCI), Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London, UK

    Leonie S. Taams, Kathryn J. A. Steel, Ushani Srenathan & Lachrissa A. Burns

  2. Department of Rheumatology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

    Bruce W. Kirkham

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All authors contributed to researching data, discussion of content, writing, and reviewing and/or editing the manuscript before submission.

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Correspondence to Leonie S. Taams.

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Competing interests

B.W.K. has received research grants from AbbVie, Eli Lilly & Co, Novartis, Roche and UCB and has been a speaker and adviser for Eli Lilly & Co, Janssen and Novartis. L.S.T. has received research support and speaker fees from GlaxoSmithKline, Novartis, Novo Nordisk A/S and UCB.

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Taams, L.S., Steel, K.J.A., Srenathan, U. et al. IL-17 in the immunopathogenesis of spondyloarthritis. Nat Rev Rheumatol 14, 453–466 (2018). https://doi.org/10.1038/s41584-018-0044-2

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