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Effects of the IL-23–IL-17 pathway on bone in spondyloarthritis

Nature Reviews Rheumatology volume 14, pages 631–640 (2018)Cite this article

Subjects

Abstract

Over the past several years, a pathophysiological role for the IL-23–IL-17 pathway in human disease has been defined. A subset of rheumatic diseases, including psoriatic arthritis (PsA) and ankylosing spondylitis (AS), are now acknowledged to be triggered by dysregulated IL-23–IL-17 pathway activation. Genetic evidence links the IL-23–IL-17 pathway to inflammation in these rheumatic diseases, and mechanistic data from mice support a functional role for IL-23–IL-17 pathway activation in the development of enthesitis and in entheseal bone formation. Furthermore, analysis of human tissue samples, as well as data from clinical trials, also supports a role for activation of the IL-23–IL-17 pathway in these diseases. The unique bone phenotype that occurs in PsA and AS is a surprising coexistence of both systemic bone loss and periosteal and entheseal bone formation and is likely to be the result of the actions of IL-23 and/or IL-17 on bone. However, the effects of these cytokines on bone cells are complex, and controversy remains regarding their exact roles in the specific bone microenvironments relevant to PsA and AS.

Key points

  • IL-23 is produced by activated myeloid cells, whereas IL-17 is predominantly produced by T cells and innate lymphoid cells.

  • Several lines of evidence support a role for the IL-23–IL-17 pathway in the pathogenesis of psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

  • Bone changes that occur in PsA and AS include systemic bone loss, articular erosions and entheseal bone formation and reflect the combined effects of IL-23 and IL-17.

  • IL-17A promotes osteoclastogenesis directly, as well as indirectly, through the production or induction of receptor-activator of nuclear factor-κB ligand (RANKL) expression, whereas the effects of IL-23 on osteoclasts are pleotropic.

  • IL-17A exhibits differential effects on the maturation of osteoblast precursor cells to osteoblasts depending upon the stage of differentiation of the cellular precursor.

  • IL-17A blockade inhibits articular bone erosion and might also retard systemic bone loss in PsA and AS and enthesophyte formation in PsA.

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Fig. 1: Effects of IL-23 and IL-17 on bone.
Fig. 2: Effects of IL-23 and IL-17 on osteoclasts and osteoblasts.
Fig. 3: Essential characteristics of IL-17-dependent forms of arthritis.

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Acknowledgements

The authors thank S. Williams for editorial assistance. The work of E.M.G. was partially supported by the Timothy and Elaine Peterson Research Fund (UMMS; P60037138450000). The work of G.S. was partially supported by the German Research Council (DFG; CRC1181).

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Nature Reviews Rheumatology thanks A. Deodhar, E. Lubberts and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Ellen M. Gravallese

  2. Department of Internal Medicine 3, Friedrich Alexander University Erlangen-Nuremberg and Universitatsklinikum Erlangen, Erlangen, Germany

    Georg Schett

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  1. Ellen M. Gravallese
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Both authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Ellen M. Gravallese.

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E.M.G. declares that she has received research funding from AbbVie and Eli Lilly. G.S. declares no competing interests.

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Gravallese, E.M., Schett, G. Effects of the IL-23–IL-17 pathway on bone in spondyloarthritis. Nat Rev Rheumatol 14, 631–640 (2018). https://doi.org/10.1038/s41584-018-0091-8

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