< Back to previous page

Project

Modulation of resident macrophages by enteric neurons in the muscularis externa

The gastrointestinal tract represents the largest interface between the environment and the organism. It is essential for digestion and absorption of nutrients, however at the same time acting as a barrier against potentially noxious ingested elements and infectious agents. Activation of a potent and specific immune response against pathogens counteracts and prevent invasion of harmful microorganisms. However, a tight control of this intestinal immune response is necessary to avoid undesired immune reactions toward the beneficial microbiota or food antigens. The balance between activation of the immune system versus tolerance therefore should be tightly regulated to maintain immune homeostasis not only to prevent chronic inflammation and tissue damage, but also to prevent lethal infections or uncontrolled growth of tumor cells.

The enteric nervous system was recently identified as a novel additional actor preserving immune homeostasis and tolerance. Our lab provided evidence that activation of enteric neurons, via electrical stimulation of the vagus nerve, suppressed intestinal inflammation, reduced cytokine expression and decreased the recruitment of inflammatory immune cells in a murine model of intestinal inflammation. We demonstrated that vagus nerve stimulation exerts its anti-inflammatory effect in the gut through the activation of enteric neurons in close contact with the resident intestinal macrophages. Neurotransmitters, cytokines and hormones released by the enteric neurons could play an important role as immunomodulators, taking into account that enteric neurons are in close apposition with immune cells. Moreover, different subsets of intestinal immune cells express various neurotransmitter receptors. We hypothesize that the enteric nervous system could modulate intestinal immunity through the release of specific neurotransmitters, such as acetylcholine.

In this project, I will investigate these interactions and their anti-inflammatory effects. By unraveling the crosstalk between immune and enteric nervous system, I hope to gain a better understanding on the role of enteric neurons as regulators of intestinal immune homeostasis. All of this will be of outmost importance to develop new therapeutic strategies to restore intestinal immune homeostasis and treat chronic intestinal inflammatory diseases such as IBD and food allergy.

Date:1 Feb 2014 →  30 Apr 2019
Keywords:neuro-immune, macrophage, enteric neurons
Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences, Gastro-enterology and hepatology, Endocrinology and metabolic diseases
Project type:PhD project