Connecting innervation and intestinal inflammation

The mucosal immune system in the gut is a complex network that needs to maintain balance between tolerance against commensal microbiota and active immunity against pathogenic microorganisms. In this balancing act, the immune system and the nervous system interact with each other. This thesis further explored this interaction. We questioned the role of neurotransmitters and innervation of the intestine, in the context of experimental colitis and inflammatory bowel disease (IBD). We focussed on IBD because it has a high disease burden, the pathogenesis is still incompletely understood, and therapies are not always effective. Understanding the connection between the nervous system and the gastrointestinal immune system will benefit the knowledge about the pathophysiology of colitis and potential ways to interfere with this neuroimmune interaction as therapeutic target. We show that besides neurons, T-cells in the intestine are a source of acetylcholine and they are involved in maintaining mucosal homeostasis and support the resolution of intestinal inflammation. In the next part, we show that the sympathetic nervous system and norepinephrine acts anti-inflammatory on innate immune cells and in the context of experimental colitis. We describe a new technique that enables us to chronically stimulate nerves in an awake animal. This technique benefits the research field of bioelectronics. Lastly, we studied the influence of the sympathetic nervous system in human IBD in a retrospective cohort and demonstrate that β-blockers increase the risk of a disease relapse in patients with IBD. This emphasises the relevance of the neuroimmune interaction in humans