Preclinical studies of spondyloarthritis Development of two novel disease models and pharmacologic targeting of the IL-17 pathway

Spondyloarthritis is the second most frequent form of chronic inflammatory arthritis. The disease can affect both the peripheral and axial joints and the immunopathology of spondyloarthritis is characterised by three pathological processes in the affected tissues: inflammation, cartilage and bone destruction and pathological new bone formation, potentially leading to complete ankylosis. Some aspects of spondyloarthritis remain difficult to study in human disease due to both accessibility/availability of target tissues (e.g. spinal biopsies) and ethical considerations. Disease progression in general, and pathological new bone formation in particular, can be slow and vary among patients. Several non-mutually exclusive translational strategies can contribute to address this issue. In this thesis, we explored the use of animal models to study the key pathological processes in spondyloarthritis, with special focus on new bone formation. The main objectives were 1) to refine and validate novel experimental models for spondyloarthritis, in particular models that recapitulate not only inflammation but also pathological new bone formation as key hallmark of the disease, and 2) to assess the role of pro-inflammatory cytokines in spondyloarthritis pathology in general and new bone formation in particular, with special focus on the TNF and IL-17 pathway.