Rheumatoid arthritis and Psoriatic arthritis are the most common forms of the inflammatory rheumatic diseases characterised by synovitis and progressive destruction of articular cartilage and bone. Angiogenesis is a primary crucial step in disease pathogenesis which facilitates the recruitment and migration of inflammatory cell types into the inflamed joint cavity. Subsequently, the synovial lining layer thickens and the sublining is infiltrated with T cells, B cells, mast cells, neutrophils, monocytes and macrophages which secrete a wide range of mediators which further exacerbate the inflammatory response, however little is known about the role of mast cells in driving the inflammatory response. Mast cells have been implicated in IgE-mediated immune responses in the context of allergic disease and defence against helminths. Recent studies in the K/BxN mouse model however, have firmly established mast cells as having a critical role in the pathogenesis of inflammatory arthritis. These findings have renewed interest in previous histological studies demonstrating a marked increase in mast cell expression in the human RA synovial sublining, in particular at sites of cartilage erosion, and their relationship to increased joint inflammation. Furthermore, mast cell derived mediators such as tryptase have been implicated in the activation of synovial fibroblasts and proteoglycan depletion. Targeted biologic agents in particular TNF inhibitors have advanced the treatment of both RA and PsA, although some patients do not respond highlighting the need for alternative therapies. The pro-inflammatory cytokine IL-17A is one such potential target. IL-17A is the first identified member of the IL-17 family, it is most closely related to IL-17F with 50% sequence homology. IL-17A has been KRX-0401 Akt inhibitor localized to T-cell rich areas in the RA synovium and overexpression of IL-17A has been detected in serum and SF samples from inflammatory arthritis patients compared to OA and healthy control subjects. Furthermore, expression of IL-17A correlates with disease activity and clinical response that can be modulated by both DMARD and TNFi therapy. In humans Th17 cells are a key source of IL-17A when activated by a number of key cytokines required for their development including TGF-b, IL-6, IL-21, IL-1 and IL-23. In addition to Th17 cells, cdT, NK, NKT and innate immune cells such as mast cells and neutrophils have been identified as sources of IL-17A in murine studies and more recently in humans. IL-17A, alone and in combination with other proinflammatory cytokines, drives ECM remodelling and cartilage destruction through the induction of MMPs. Hypoxia has been implicated in RA pathogenesis, previous studies have demonstrated that the level of oxygen in SF from patients with RA is reduced compared to healthy controls. Low oxygen levels have been reported in tenosynovium from RA patients with tendon rupture. More recently we have demonstrated profound hypoxia in inflamed ST using an oxygen sensing probe in vivo, levels of which were inversely associated with synovial inflammation and blood vessel morphology Several studies using synovial cells.