Project 455135

Our intestine forms a barrier to the outside world. Due to its proximity with the environment, the intestine is highly susceptible to infections and injury. The intestinal barrier is composed of a single layer of epithelial cells, which are rapidly replaced when damaged by the immense replicating ability of intestinal stem cells. This regeneration forms the foundation of the intestine's defensive strategy allowing it to repair itself after injury and tolerate damage imposed by chronic infections. Immune cells form another essential component of the intestinal barrier and defence. However, how immune cells support the regenerative capacity of intestinal stem cells to promote tissue repair and disease tolerance following injury remains unknown. The goal of this proposal is to characterize the immune cell population(s) that drive epithelial stem cell reprogramming and decipher the molecular mechanisms by which barrier integrity is restored during tissue damage. To investigate this dynamic interaction, our group uses an intestinal parasitic helminth that damages the intestinal epithelium and disrupts the epithelial reparative mechanisms. We recently identified that during the tissue injury phase, this helminth activates a unique immune cell population that may influence epithelial repair. In the aims of this proposal, this immune cell population will be deeply characterized to identify how it orchestrates intestinal epithelial repair, specifically through its action on intestinal stem cells. Overall, this proposal will uncover new mechanisms of immune-epithelial intestinal cross-talk that could be exploited for novel intestinal regenerative therapies beneficial in infections, inflammatory bowel diseases and clinical radiation therapy.