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

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 95; no. 7; pp. 779 - 787
• Main Authors: Heftdal, Line Dam, Andersen, Thomas, Jæhger, Ditte, Woetmann, Anders, Østgård, René, Kenngott, Elisabeth E., Syrbe, Uta, Sieper, Joachim, Hvid, Malene, Deleuran, Bent, Kragstrup, Tue W.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2017; Springer Nature B.V
• Subjects: Actin; Adult; Aged; Arthritis; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cells, Cultured; Enzyme-linked immunosorbent assay; Female; Fibroblasts - immunology; Fibroblasts - pathology; Flow cytometry; Helper cells; Human Genetics; Humans; Inflammation; Inflammatory diseases; Interleukins - analysis; Interleukins - blood; Interleukins - immunology; Internal Medicine; Joint diseases; Leukocytes (mononuclear); Lymphocytes T; Male; Middle Aged; Mineralization; Molecular Medicine; Original Article; Osteoblasts; Osteoblasts - immunology; Osteoblasts - pathology; Osteogenesis; Plasma; Rheumatic diseases; Secretion; Smooth muscle; Spondylarthritis - blood; Spondylarthritis - immunology; Spondylarthritis - pathology; Synovial fluid; Synovial Fluid - cytology; Synovial Fluid - immunology; Synoviocytes; Synoviocytes - immunology; Synoviocytes - pathology; Synovium; Th17 Cells - immunology; Th17 Cells - pathology; Tumor necrosis factor; Tumor Necrosis Factor-alpha - immunology; Vitamin D; Young Adult; Fibroblasts; IL-26; TNF-α; Spondyloarthritis; Osteoblasts
• ISSN: 0946-2716; 1432-1440; 1432-1440
• DOI: 10.1007/s00109-017-1528-2

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.