The gut tissue is rich in immune cells that are in close contact with a wide range of antigens derived from nutrients and microbiota, making the gut the primary source of non-self-antigens in our body. We would like to investigate the role of epithelial cells in instructing the gut mucosal immune system.
One example is of MHCII+ intestinal stem cells (ISCs) which can act as non-conventional antigen-presenting cells (APCs). Lgr5+ ISC-mediated presentation could thus provide an alternate mechanism by which the epithelial barrier can sense and initiate a response to signals coming from the lumen. We would like to further explore these findings by manipulation of the epithelial and immune cells within the gut.
MHCII+ epithelial cells may play a direct role in immune tolerance vs. activation to discrete luminal antigens. We aim to characterize the effect of epithelial MHCII on the T cell receptor (TCR) repertoire of the lamina propria T cells. To do so, we will use in vitro and in vivo T cell tolerance and activation assays and explore the impact of epithelial MHCII deletion on resident T cells in the gut. Our goal is to expand our knowledge of T cell education in the gut by ISC.