title: Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis.
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.
  
  
  
  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.
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000, Aarhus C, Denmark.
authors.forename: Line Dam
authors.initials: LD
authors.lastname: Heftdal
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000, Aarhus C, Denmark.|Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Andersen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c, 2200, Copenhagen N, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Jæhger
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c, 2200, Copenhagen N, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.affiliation: Department of Rheumatology, Regional Hospital Silkeborg, Falkevej 1-3, 8600, Silkeborg, Denmark.
authors.forename: René
authors.initials: R
authors.lastname: Østgård
authors.affiliation: Department of Gastroenterology, Infectiology, and Rheumatology, Charité Universitätsmedizin Berlin, 12200, Berlin, Germany.
authors.forename: Elisabeth E
authors.initials: EE
authors.lastname: Kenngott
authors.affiliation: Department of Gastroenterology, Infectiology, and Rheumatology, Charité Universitätsmedizin Berlin, 12200, Berlin, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Syrbe
authors.affiliation: Department of Gastroenterology, Infectiology, and Rheumatology, Charité Universitätsmedizin Berlin, 12200, Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000, Aarhus C, Denmark.|Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200, Aarhus N, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000, Aarhus C, Denmark. bd@biomed.au.dk.|Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark. bd@biomed.au.dk.|Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200, Aarhus N, Denmark. bd@biomed.au.dk.
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000, Aarhus C, Denmark.|Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
authors.forename: Tue W
authors.initials: TW
authors.lastname: Kragstrup
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000032:analysis* / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000276:immunology / Q000473:pathology; D010012:Osteogenesis; D025241:Spondylarthritis / Q000097:blood / Q000276:immunology / Q000473:pathology*; D013582:Synovial Fluid / Q000166:cytology* / Q000276:immunology; D000070918:Synoviocytes / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: C406767:IL26 protein, human; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha
keywords: Fibroblasts; IL-26; Osteoblasts; Spondyloarthritis; TNF-α