Phagocytes, NADPH oxidases and immunogenetics in systemic inflammation
We are interested in the molecular and cellular mechanisms of inflammation, in particular the regulation of reactive oxygen species (ROS) production by the NADPH oxidases (NOX) in phagocytes and epithelial cells. Although ROS production by phagocytes is necessary for host defense against pathogens, excessive and inappropriate ROS production can induce severe tissue injury that participates to the physiopathology of inflammatory diseases. So far only limited information is available as to how ROS production becomes out of control in inflammatory diseases. The aim of our work is to study the mechanisms underlying normal and pathological inflammatory responses, particularly the regulation of the phagocyte NADPH oxidase NOX2 and its epithelial homologue NOX1.
Our work is conducted following three main axis : 1) to study the mechanisms regulating NOX2 activation in phagocytes (neutrophils, monocytes, macrophages and dendritic cells) and NOX1 in epithelial cells in response to pro- and anti-inflammatory agents; 2) to study the role of NOX2 and NOX1 in inflammatory process by investigating their activation in human phagocytic disorders, human inflammatory diseases and in animal models of inflammation ; 3) to identify bio-markers and develop pharmacological tools for therapeutic purposes.