Grant: Doctoral Research Award - PA: Digestive Health (SHOPP)

Inflammatory bowel disease (IBD) is an unexpected inflammatory response in the gut. The incidence of IBD is steadily increasing in western populations; therefore it is necessary to study this disease since there is still no definitive cure. Immune cells such as dendritic cells (DC) have been implicated in the development of IBD. These cells are thought to recognize the commensal bacteria through pattern recognition receptors but instead of producing an anti-inflammatory response to the beneficial flora, a pro-inflammatory response is initiated. Although the inflammatory response is thought to occur when immune cells in the intestine recognize the normal bacteria in the gut as foreign, why this occurs is still unclear. Helminths (worms) are another interesting infection of the intestinal immune system. While there are effective treatments for worms, curing people of worms has resulted in the increase of IBD. Recently, there has been evidence that a worm infection in the gut results in decreased expression of pattern recognition receptors on DCs specific to that parasite. As a result, the worm is able to persist and survive while causing various complications to its host. Our lab has shown that the absence of the protein CD45 on DCs increases the secretion of pro-inflammatory cytokines when certain pattern recognition receptors on DCs are stimulated. We have already shown that in an animal model of chronic IBD, the absence of CD45 decreases the severity of systemic disease. We will continue to study the role of CD45 in other models of IBD to best mimic all aspects of human IBD. We predict that in these acute models, the severity of IBD will be more severe in CD45 deficient mice. We will also study the role of CD45 on innate immune cells in helminth infection and predict that CD45 deficient mice will be more resistant to helminthes due to a protective T cell response in the mucosa of these mice.