Intestinal stem cells (ESCs) are well-characterized adult stem cells. However, their contribution to mucosal immunity is less appreciated. We are now exploring the role of intestinal stem cells in innate and adaptive immune responses that may lead to gut homeostasis or when disrupted to a wide array of diseases. Our toolbox includes in vitro gut organoids, spheroids and monolayers and in vivo mouse models.
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.
Dysfunction of the epithelial barrier may lead to Inflammatory Bowel Diseases (IBD), commonly separated into two major diseases: Chron's disease and Ulcerative colitis. We are interested in understanding disease mechanisms that are playing a role in these diseases with an emphasis on uncovering the role of hundreds of known risk genes, many of them with unknown function.