The main function of the intestinal epithelium is to absorb nutrients from food, but it also serves as a barrier to protect the body from harmful pathogens, chemicals, and food antigens. To aid in its protection, the epithelial layer is patrolled by an unconventional pool of T lymphocytes called intraepithelial lymphocytes (IEL). Despite being one of the largest subsets of T cells, we understand very little of how these cells are maintained in quiescence at homeostasis; are activated in the presence of external insults, how they are fueled and how they respond. Research in my lab aims to define the how IEL coordinate responses to chemical, dietary and microbial inputs at the intestinal epithelium. Using a novel mouse model that for the first time permits inducible depletion of all IEL, we are establishing the role of IEL in infection and intestinal homeostasis and determining the importance of IEL metabolism as the crucial link between diet, IEL function and intestinal responses.