Neutrophils are cells of the innate immune system. In immune-mediated diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD), they drive the disease, by acting as a source of autoantigens, inflammatory cytokines and cytotoxic agents. Of note, neutrophils are heterogeneous with different activation thresholds and effector functions across organs and patients. We hypothesize that these differences are associated with treatment resistance in RA, SLE, and IBD. To test this hypothesis, we will characterize the gene expression, surface markers, and effector functions of neutrophils from patients who respond to therapy and those who do not in cell culture as well as in humanized mouse models of arthritis and IBD. We will further investigate the role of candidate markers that modulate neutrophil activation thresholds in inflammation propagation and therapy resistance.
Principal Investigators
Prof. Dr. med. Ricardo Grieshaber-Bouyer