Targeting intestinal macrophages as new treatment for Inflammatory Bowel Disease. IBD-MAC.

The intestinal immune response is tightly regulated to prevent aberrant immune activation towards food antigens and symbiotic microflora, to which the gastrointestinal tract is continuously exposed. In individuals with a genetic and/or environmental predisposition, this regulation is impaired leading to chronic intestinal inflammation, which may result in Inflammatory Bowel Disease (IBD). Recent evidence indicates that intestinal macrophages (Mϕs) are gatekeepers of the intestinal immune homeostasis. Consequently, the focus in IBD research has recently shifted from the adaptive immune system towards the study of mucosal innate immune responses, including monocyte/Mϕ function transitions. In this respect, we have identified various drug candidates for repurposing, as well as a peptide, activating a metabolic checkpoint enzyme, thereby steering Mϕ toward anti-inflammatory status. In line, our preliminary data indicate that the most promising drug significantly decreases IBD readouts in a mouse model of colitis. With this C3 project, we aim at establishing solid preclinical datasets as a basis to file (a) patent application(s) and explore licensing opportunities with interested companies in the IBD domain.

Keywords:Inflammatory Bowel Disease, Intestinal macrophages, drug repurposing, mucosa regeneration, metabolic checkpoint enzyme

Disciplines:Inflammation, Gastro-enterology