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Smoking is a major risk factor for the development of RA. The mechanisms by which smoking influences the development of RA is however still unclear. To better understand how smoking confers the risk to develop RA, we use an in vitro model of smoke exposure together with an in vivo mouse model and human data. In all three systems, we found profound changes in gene expression of synovial fibroblasts induced by cigarette smoke. Therefore, we further analyse the specific factors and mechanisms that are involved in the response of synovial fibroblasts to cigarette smoke and how these are connected to disease development.