LAUSR

Spondyloarthritis (SpA) is a term that refers to a group of inflammatory diseases that includes psoriatic arthritis, axial SpA and nonradiographic axial SpA, reactive arthritis, enteropathic arthritis and undifferentiated SpA. The disease subtypes share clinical and immunological features, including joint inflammation (peripheral and axial skeleton); skin, gut and eye manifestations; and the absence of diagnostic autoantibodies (seronegative). The diseases also share genetic factors. The aetiology of SpA is still the subject of research by many groups worldwide. Evidence from genetic, experimental and clinical studies has accumulated to indicate a clear role for the IL-17 pathway in the pathogenesis of SpA. The IL-17 family consists of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F, of which IL-17A is the best studied. IL-17A is a pro-inflammatory cytokine that also has the capacity to promote angiogenesis and osteoclastogenesis. Of the six family members, IL-17A has the strongest homology with IL-17F. In this Review, we discuss how IL-17A and IL-17F and their cellular sources might contribute to the immunopathology of SpA.Evidence from genetic, experimental and clinical studies has accumulated to indicate a role for the IL-17 pathway in the pathogenesis of spondyloarthritis. This Review discusses how IL-17A and IL-17F and their cellular sources contribute to the immunopathology of these diseases.Key pointsGenetic and animal model studies indicate that the IL-23–IL-17 axis is involved in the pathogenesis of spondyloarthritis (SpA).IL-17A has been identified directly in the blood and synovial fluid of patients with SpA, with T cells representing a key source of this cytokine.IL-17A and IL-17F act in synergy with other pro-inflammatory mediators to induce pro-inflammatory responses across a range of cell types.IL-23–IL-17-targeted therapies have been shown to be effective in psoriatic arthritis and ankylosing spondylitis.Increased understanding of the pathogenic role of the IL-23–IL-17 axis, the cellular sources of these cytokines and their molecular regulation in SpA is essential to develop novel therapeutic strategies that target this pathway.