Neutrophils and Vasculitis
The research project of the team explores the biology of neutrophil which is a key cell in inflammation and in the defense against bacteria. However, if activated neutrophils are not properly eliminated, they can damage the host tissues.
Our team studies neutrophils in autoimmune vasculitis because they play a pivotal role in the immune dysregulation and in the destruction of small vessels. The team is also focused on the role of neutrophils in the pulmonary inflammation associated with cystic fibrosis.
The new mechanisms in the control of neutrophil activation that we uncover could be relevant in other diseases in which neutrophils are involved like in arthritis, septic shock, cancer and COVID-19.
Autoimmune vasculitides associated with anti-neutrophil cytoplasmic antibody (called ANCA) are examples of systemic inflammation in which the persistence of activated neutrophils at the site of inflammation hinders the resolution of inflammation leading to small vessel necrosis.
The team examines the biology of neutrophils to understand their effector mechanisms (particularly the oxidants and the proteinases) associated with the signalling pathways regulating different types of death (Research project 1). Our work is also focused on the structural and functional study of proteinase 3, the target antigen of ANCA (Research project 3). The proteinase 3 expressed at the surface of apoptotic neutrophils is considered as a « danger signal » by macrophages thereby stimulating innate immunity (Research project 2). Interactions between immune and vascular cells (endothelial cells, smooth muscle vascular cells) are involved in the inflammation and the vascular remodeling are also studied (Research project 4).
The team benefits from the very specific recruitment of patients with systemic vasculitis of the “National reference center for systemic vasculitidis and systemic sclerosis” at Cochin Hospital. In addition the strong clinical interface with the Department of Internal Medicine at the Cochin Hospital as well the interactions with other clinical Departments, particularly with the Pneumology Department (CLIC : for our investigations of neutrophils in cystic fibrosis patients), are positive points to carry out our multidisciplinary project involving both basic and translational research.