IL-17A expression is localised to both mononuclear and polymorphonuclear synovial cell infiltrates

• Published in: PloS one 2011-08, Vol.6 (8), p.e24048-e24048
• Main Authors: Moran, Ellen M, Heydrich, René, Ng, Chin Teck, Saber, Tajvur P, McCormick, Jennifer, Sieper, Joachim, Appel, Heiner, Fearon, Ursula, Veale, Douglas J
• Format: Article
• Language: English
• Subjects: Arthritis; Arthroscopy; B cells; Biology; Biopsy; CD4 antigen; Cell culture; Cell Movement - immunology; Cytokines; Disease; Fibroblasts; Gene expression; Humans; Hypoxia; Immunofluorescence; Immunohistochemistry; In vivo methods and tests; Infiltration; Inflammation; Inflammation - pathology; Interleukin 6; Interleukin-17 - analysis; Joints - metabolism; Leukocytes; Leukocytes (mononuclear); Leukocytes (neutrophilic); Leukocytes (polymorphonuclear); Leukocytes, Mononuclear - chemistry; Ligands; Lymphocytes; Lymphocytes T; Mast cells; Measurement methods; Medicine; Morphology; Multiple sclerosis; Neutrophils; Neutrophils - chemistry; Oxygen; Pathogenesis; Peripheral blood; Rheumatoid arthritis; Rheumatology; Serum levels; Studies; Synovial Fluid; Synovial Membrane - pathology; Synovium; T cells; Tryptase; Vascular endothelial growth factor; White blood cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024048

This study examines the expression of IL-17A-secreting cells within the inflamed synovium and the relationship to in vivo joint hypoxia measurements. IL-17A expression was quantified in synovial tissue (ST), serum and synovial fluid (SF) by immunohistochemistry and MSD-plex assays. IL-6 SF and serum levels were measured by MSD-plex assays. Dual immunofluorescence for IL-17A was quantified in ST CD15+ cells (neutrophils), Tryptase+ (mast cells) and CD4+ (T cells). Synovial tissue oxygen (tpO(2)) levels were measured under direct visualisation at arthroscopy. Synovial infiltration was assessed using immunohistochemistry for cell specific markers. Peripheral blood mononuclear and polymorphonuclear cells were isolated and exposed to normoxic or 3% hypoxic conditions. IL-17A and IL-6 were quantified as above in culture supernatants. IL-17A expression was localised to mononuclear and polymorphonuclear (PMN) cells in inflamed ST. Dual immunoflourescent staining co-localised IL-17A expression with CD15+ neutrophils Tryptase+ mast cells and CD4+T cells. % IL-17A positivity was highest on CD15+ neutrophils, followed by mast cells and then CD4+T-cells. The number of IL-17A-secreting PMN cells significantly correlated with sublining CD68 expression (r = 0.618, p