"Chronic inflammation is a common feature in diseases like primary immunodeficiencies and autoimmunity. It is the consequence of the inability of the immune system to regulate and resolve the inflammatory process. Even though significant advances have been made in the past years to understand some of the mechanisms involved in chronic inflammation, which lead to the development of therapeutic strategies based on biologicals, there are still no successful therapies to fully stop the chronic inflammatory process.It is widely assumed that reactive oxygen species are part of the pro-inflammatory process, and are believed to be active players in the destructive processes associated with chronic inflammation. Therefore, the prescription of anti-oxidants has flourished in the past years. However, more evidence is being gathered from human and animal studies, that reactive oxygen species might have a regulatory effect associated with the resolution of inflammation and tolerisation of B and T cells. A significant example comes from patients with chronic granulomatous disease, which have mutations in the proteins of the NADPH-oxidase complex, which impair the production of reactive oxygen species. These patients and family members have more tendency to develop autoimmune conditions. Also, a recent model of chronic arthritis has been developed in mice and rats with defects in the production of reactive oxygen species due to a mutation in the Ncf1 gene of the NADPH-oxidase complex.Using a combination of human samples from patients with chronic inflammatory diseases and animal models of chronic inflammation, the present proposal aims at exploring the role of the NADPH-oxidase complex and the production of reactive oxygen species in the context of chronic inflammation."