The role of myeloid cells in the resolution of intestinal inflammation

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract leading to debilitating symptoms such as bloody diarrhea, fatigue and weight loss. To date, no resolutive therapies are available for IBD, resulting in an invaluable impact on the health, emotional, financial and social state of the patients and their families. Although most studies on IBD over the last decades have looked into abnormal adaptive immunity, the focus has recently shifted towards an interest in alterations of the mucosal innate immune response. Recent data suggest a causal link between defects in the resolution of intestinal inflammation associated with impaired bacterial clearance, excessive cytokine secretion and altered monocyte to macrophage (Mφ) transition in patients with IBD. In line, our data indicates that resolution of intestinal inflammation is dependent upon a specific subpopulation of monocyte-derived Mφs with pro-resolving properties. However, despite significant advances in our understanding of Mφ regulation and function during inflammation, it is not clear how pro-resolving Mφ exert their tissue protective functions and which factors influence monocyte differentiation toward a proresolving phenotype in the gut. To answer these questions, we will combine state of the art transgenic mouse models of intestinal inflammation with single cell RNA sequencing to identify the molecules and pathways involved in the differentiation and function of pro-resolving Mφs. Unravelling the mechanisms favouring pro-resolving Mφs generation will representing a major breakthrough in our understanding of intestinal inflammation and it will be of crucial importance to develop novel therapeutic strategies in our fight against IBD.