UNTANGLED · Unravelling neuroimmune crosstalk to find novel treatment targets for inflammatory bowel disease

Up to 40% of patients with inflammatory bowel disease (IBD) do not respond to standard of care treatment with anti-inflammatory drugs. Unfortunately, the mechanisms driving persistent inflammation are unknown, resulting in a lack of specific therapies and an important burden for patients and society. Enteric neurons are highly specialized cells that sense and respond to nutrients, microbial products and inflammatory signals and densely innervate the gut. Besides regulating gastrointestinal motility, emerging studies indicate that crosstalk between enteric neurons and immune cells regulates inflammation, tissue homeostasis and antimicrobial immunity. However, this has not been investigated in the context of IBD. I hypothesize that enteric neurons become rewired during IBD and acquire an inflammatory signature that amplifies inflammation. Recent technological advancements will allow the investigation of enteric neurons via the use of cutting-edge tools in microfluidic droplet generation, molecular biology and functional genomics. We will leverage the Xavier lab’s expertise in the field of the enteric nervous system at the Broad Institute of MIT and Harvard during the outgoing phase, the expertise of Dr. D’Haens in IBD during the return phase at the Amsterdam University Medical Center and my expertise in pre-clinical IBD models in vitro and in vivo to characterize the role of enteric neurons in IBD for the first time and find potential treatment targets.