GM-CSF-mediated molecular signalling pathways contributing to inflammation
GM-CSF is a pro-survival factor for monocytes, macrophages and granulocytes, and can activate them for enhanced inflammatory mediator levels. Depletion of GM-CSF has been shown to suppress arthritis in animal models. Clinical trials in rheumatoid arthritis (RA) targeting GM-CSF or its receptor have reported success in Phase II, although its mode of action remains unknown. Recent data from our laboratory suggested that a GM-CSF regulated chemokine CCL17 could be critical for the pro-inflammatory actions of GM-CSF. This project will investigate whether GM-CSF-mediated CCL17 production contributes to the inflammatory cytokine production in RA synovium and synovial macrophages/dendritic cells.