Uncovering Enteric glia-macrophage communication in the intestinal homeostasis and inflammation.

One of the main tasks of the immune system is to appropriately react to “danger” or “non-danger” signals. This is even more relevant in the intestine, where immune cells are constantly presented with foreign substances as food. Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homoeostasis and to prevent indiscriminate immune activation against the gut content. Loss of this delicate equilibrium results in many intestinal disorders such as inflammatory bowel disease and allergies. To better understand how intestinal homoeostasis is preserved, we will investigate how immune responses are modulated and controlled in the gut. In this project, we will examine the role of an important player in this system: enteric glial cells. Enteric glial cells, the prevalent constituent of the nervous system in the gut wall, have been traditionally considered only as supportive cells surrounding enteric neurons. Using a novel experimental co-culture approach developed in our laboratories, we have obtained preliminary data showing that enteric glia can modulate the inflammatory response. However, how enteric glia communicates with the immune system remains still to be addressed. Understanding the molecular mechanisms by which mucosal immune cells and the enteric glia crosstalk in health and disease will help us to develop novel therapeutic strategies to treat intestinal immunemediated diseases.