In our study we showed that IL-17A expression was localized to tryptase+ mast cells, CD15+ neutrophils and CD4+T cells, with highest expression observed on CD15+ neutrophils. The expression of IL17A on several cell subtypes within the synovium, suggest it plays an important immune-modulatory role. Our data is consistent with recent reports in psoriasis skin biopsies showing similar IL17A expression patterns. Furthermore, IL-17A+ PMN cells correlated with sublining CD68 expression which again supports previous studies that demonstrate mast cells can HhAntag691 activate resident synovial macrophages via the production of various proinflammatory mediators and recruit both neutrophils and monocytes into the joint. IL-17A is a well established mediator of angiogenesis and inflammatory cell influx via the production of cytokines and chemokines. The expression of IL-17A by these cells further implicates the pivotal role IL17A plays in the pathogenesis of RA. In addition we demonstrated that in vivo measures of hypoxia were associated with synovial mononuclear IL-17A expression. This is supported by previous studies demonstrating the effect of hypoxia on immune cells. Studies in both human and murine tissue have shown T cell accumulation in hypoxic tissue, and its expression has been previously shown to be associated with hypoxia. Exposure of murine CD3+ T cells to hypoxia enhances T cell expression, proliferation and activation in a HIF-1a dependent manner. We have previously shown that low hypoxia is inversely associated with synovial mononuclear cell infiltrates, vascularity and others have shown that HIF1a is co-localised to synovial mononuclear cells in the joint, and with potent chemotactic factors macrophage inflammatory protein CCL20 and Stromal cell derived factor-1 and angiogenesis. Hypoxia enhances amyloid beta peptide induced IL-17A production and TH-17 differentiation in PBMC cultures. Normally neutrophils have a short half-life and rapidly undergo apoptosis; however following exposure to hypoxia neutrophil apoptosis can be suppressed. While we found no increase in the number of IL-17A+ mast cells in patients with low tpO2 levels, previous studies suggest mast cells respond early to hypoxic insult in rat models of cerebral ischemia. Exposure to hypoxia has increased production of MMPs and tryptase by mast cells leading to tissue degradation. The expression of IL-17A and its receptor are upregulated in both murine and human ischemic tissue compared to non ischemic tissue. Murine mast cells have been shown to produce IL-17A in response to stimulation with TLR2 ligands. Furthermore, human mast cells have been shown to stimulate activated T cells suggesting a potential role in TH-17 differentiation. Mast cells have been shown to be early responders to a hypoxic insult and degranulation of mast cells can be detected histologically 1–2 hours after the initiation of arthritis in the K/BxN model. In this study while IL-17A expression was associated with low pO2 levels and hypoxia induced IL-6 expression in vitro, no effect on IL-17A expression in vitro was observed.