Myeloid effector cells in inflammation (360G-Wellcome-207144_Z_17_Z)

Dysregulation of inflammation underlies a range of chronic inflammatory disease. By increasing our understanding of inflammatory mechanisms we may be able to identify specific therapeutic targets to treat disease. Using a murine model of acute, resolving inflammation, with zymosan as stimulus, we create a physiological inflammatory system where we can observe the spatiotemporal relationship of monocytes, macrophage and neutrophils which predominate this response. These observations in a controlled setting will give us insights into how these cells interact to orchestrate an inflammatory response. Gain of function IRF5 is associated with a range of autoimmune and inflammatory disease and promotes an pro-inflammatory phenotype in monocytes and macrophages. We will manipulate the system using mice deficient of IRF5 to modulate the monocytes phenotype and will be able to study the impact on neutrophil function and activation. These findings have the potential to be translated into more complex physiological systems and present new pathways for the study of disease.