Decoding macrophage functional heterogeneity in the pathogenesis of Crohn's disease

Crohn's disease is a lifelong, incurable, debilitating condition of unknown cause, characterised by repeated episodes of bowel inflammation. Modern therapy incompletely treats inflammation such that <50% of patients have complete bowel healing despite treatment, with many more patients becoming resistant to treatment over time. Intestinal macrophages are increasingly thought to be key mediators of these inflammatory processes in CD, but paradoxically also have numerous beneficial roles in the healthy gastrointestinal tract. Thus, exploring how subtypes of macrophage drive inflammation in CD may lead to more specific and novel therapies. Once key pathways and subsets are identified, I will use animal models of intestinal inflammation to show the precise function of these cells. By completing this research, I will have characterised the intestinal macrophage composition in health and in CD, how this changes over time and how this can be targeted to promote prompt resolution of inflammation.