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Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis

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Abstract

Spondyloarthritis (SpA) is characterized by inflammation and new bone formation and can be treated by inhibition of the proinflammatory cytokines TNF-α and IL-17A. IL-26 is considered a proinflammatory cytokine, predominantly related to Th17 cells. In the present study, we investigate IL-26 expression in SpA patients, and examine the in vitro production of IL-26 by synovial cells and the effects of IL-26 on human osteoblasts. IL-26 was measured by ELISA in plasma and synovial fluid (SF) of 15 SpA patients and in plasma samples from 12 healthy controls. Facet joints from axial SpA patients were stained for IL-26 and analyzed by fluorescence microscopy. Synovial fluid mononuclear cells, C-C motif chemokine receptor 6 memory Th17 cells, and fibroblast-like synoviocytes (FLSs) were isolated, and supernatants were analyzed for IL-26 content by ELISA. FLSs were further stained for IL-26 production and the myofibroblast marker α-smooth-muscle-actin (αSMA) and analyzed by flow cytometry. Human osteoblasts were cultured in the presence of IL-26, and the degree of mineralization was quantified. We found that IL-26 levels in SF were increased compared with plasma (P < 0.0001). Moreover, IL-26 expression was found in facet joints of axial SpA patients within the bone marrow. IL-26 secretion was primarily found in αSMA+ myofibroblasts. In contrast, Th17 cells did not produce detectable amounts of IL-26. Human osteoblasts treated with IL-26 showed increased mineralization compared with untreated osteoblasts (P = 0.02). In conclusion, IL-26 seems to be produced by myofibroblasts in the inflamed synovium and could be a possible facilitator of bone mineralization in SpA.

Key messages

  • IL-26 levels are higher in synovial fluid compared to plasma in spondyloarthritis.

  • IL-26 was identified in axial facet joints of spondyloarthritis patients.

  • Myofibroblasts from the spondyloarthritis synovium produce large amounts of IL-26.

  • IL-26 induces bone mineralization in human osteoblasts.

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Acknowledgements

This work was supported by unrestricted grants from The Novo Nordisk Foundation and The Danish Rheumatism Association. Flow cytometry and cell sorting were performed at the FACS Core Facility, Aarhus University, Denmark.

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Authors and Affiliations

  1. Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000, Aarhus C, Denmark

    Line Dam Heftdal, Thomas Andersen, Malene Hvid, Bent Deleuran & Tue W. Kragstrup

  2. Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark

    Thomas Andersen, Bent Deleuran & Tue W. Kragstrup

  3. Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c, 2200, Copenhagen N, Denmark

    Ditte Jæhger & Anders Woetmann

  4. Department of Rheumatology, Regional Hospital Silkeborg, Falkevej 1-3, 8600, Silkeborg, Denmark

    René Østgård

  5. Department of Gastroenterology, Infectiology, and Rheumatology, Charité Universitätsmedizin Berlin, 12200, Berlin, Germany

    Elisabeth E. Kenngott, Uta Syrbe & Joachim Sieper

  6. Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200, Aarhus N, Denmark

    Malene Hvid & Bent Deleuran

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  1. Line Dam Heftdal
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Correspondence to Bent Deleuran.

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All patient samples were obtained after written consent and the collection of samples were approved by the Central Denmark Region Committee on Biomedical and Research Ethics (project number 20121329), the Danish Data Protection Agency, and the Good Clinical Practice unit at Aarhus University.

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The authors declare that they have no conflicts of interest.

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Heftdal, L.D., Andersen, T., Jæhger, D. et al. Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis. J Mol Med 95, 779–787 (2017). https://doi.org/10.1007/s00109-017-1528-2

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  • DOI: https://doi.org/10.1007/s00109-017-1528-2

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