Lay Summary

Inflammatory bowel disease (IBD) is caused by immune cells that mistakenly consider self-intestinal tissue as foreign, and therefore commence an autoimmune attack on the gut. There have been many therapeutic attempts to modulate the immune response, and in some instances eliminate self-reactive immune cells. However, no therapy has been able to induce tolerance to intestinal tissue and prevent further destruction. One exciting new avenue for treatment is cell-based tolerogenic therapy, whereby the infusion of specific cell types can delete or “re-educate” the immune system to self. The central question remains: which cell type? Many elegant studies have recently shown that there are endogenous cells within the body whose function is to display self molecules to the immune system in order to maintain self-tolerance in vivo. We have discovered that mouse and human mesenchymal stem cells (MSCs) express self protein antigens and can maintain this expression during ex vivo expansion, unlike other self antigen expressing cells. Given this ability to express self antigens and presumably induce tolerance, we hypothesized that MSCs can be a very specific and targeted treatment for IBD. The purpose of this project is to evaluate self-antigen presentation as a primary mechanism of action by MSC grafts in the treatment of mouse models of IBD. We will employ cutting edge immunological, gastroenterological and radiological methods to develop an effective stem cell-based therapy for IBD and evaluate the specificity of this treatment and potential side-effects. This research program intends to essentially create a new drug class based on antigen-specific stem cell grafts for IBD therapy.