Regulation of Enteric Nervous System Function by Group 3 Innate Lymphoid Cells

PROJECT SUMMARY The enteric nervous system (ENS) is critical for controlling key intestinal functions such as peristalsis and nutrient absorption. Emerging paradigms indicate that interactions between neurons and immune cells fundamentally impact immunity and inflammation in peripheral tissues. Recently, it has been shown that the ENS can act on the intestinal immune system to modify the function of innate lymphoid cells (ILCs). However, despite these advances, the role of ILCs in ENS function remains unexplored. In my preliminary studies, I defined that ILCs are genetically poised to interact with the ENS and support their development or function. By examining a specific factor produce by ILCs, I defined how it is regulated and developed a lineage-specific knockout to demonstrate this pathway plays a role in augmenting the ENS. To goals of this proposal are, in Aim 1, to utilize in vivo and ex vivo models to determine the molecular mechanisms that regulate ILCs and associated factors, and, in Aim 2, to determine the cellular mechanisms by which ILC-derived factors impacts the ENS and the importance of this interaction in maintaining ENS homeostasis during inflammation. Collectively, these two aims will critically define a novel molecular mechanism by which ILCs impact ENS function in states of intestinal health and disease, which could provoke novel preventative, therapeutic or curative strategies. Further, it will create an outstanding training opportunity for my continued development in science and eventual transition to become an independent academic researcher.