Metabolic regulation of intraepithelial T lymphocyte responses to intestinal infection

In response to intestinal infection, intraepithelial T cells (IEL) mobilise their arsenal to protect the gut. This process involves several energy-consuming processes including secretion of effector molecules and increased surveillance. IEL reside between nutrient-absorptive intestinal epithelial cells, and are also exposed to microbes and the anaerobic lumen of the gut. I aim to investigate how IEL get their energy to survive and fuel immune responses in this nutritionally unique environment. Using genetic models to investigate and modulate IEL metabolic pathways, high-resolution respirometry to study mitochondrial respiration, metabolomics, and multidimensional flow cytometry, we will explore how IEL responses are metabolically regulated, both at steady-state and during intestinal infection. We will investigate the signalling pathways that drive the metabolic changes during activation of IEL. These studies will clarify how IEL immunometabolic responses are tailored to the gut environment and will inform future studies of how diet and microbes regulate intestinal immune responses.