Objective: To delineate the biological and molecular pathways that initiate and drive chronic inflammatory disease and to transform the knowledge obtained into the development of novel anti-inflammatory interventions. Focus will be given to Rheumatoid Arthritis (RA) since longitudinal data indicate that intensive treatment can prevent persistency and chronicity. State of the Art and beyond: The first generation of targeted therapies in chronic inflammatory disease used RA as prototype disease for clinical development. These therapies are now also used in other inflammatory disorders. Although treatments have been developed that are effective in a proportion of patients, they are aspecific, relatively toxic and do not mediate cure. Currently, it is unknown which molecular effects need to be induced and/or targeted to prevent induction or persistency of RA. However, this is within reach through a strong international consortium of world-leading European groups that cover both basic- and translational research. Work plan: The general strategy for the project is to enable parallel studies that are focussed on critical switch moments in the biological processes that drive chronicity of inflammation. As the consortium consists of a multidisciplinary team with basic- and clinical expertise, translational research will be conducted to delineate the molecular basis of dysregulated inflammation, the RA-specific autoimmune-response and organ specific pathobiology. The final aim is to develop novel- and specific anti-inflammatory therapies. Impact of the project: This project will (i) identify the molecular networks underlying chronic inflammation and thereby (ii) will define novel targets for drug-development as well as (iii) algorithms that will predict outcome of therapy. Moreover, within this project European SMEs will evaluate new interventions (iv) and this project will (v) offer a platform to rapidly develop ideas and patents into new therapies.