Crohn’s & Colitis Congress™

Sessions Speakers Exhibitors Floor Plan Buzz

P212 - NOVEL ROLE OF INTESTINAL GOBLET CELLS IN INDUCTION OF TOLERANCE AND PROMOTING STABILITY OF REGULATORY T CELLS (Room Poster Hall)

Background: Mucosal tolerance towards luminal antigens is a process fundamental to intestinal homeostasis, the breakdown of which results in onset of inflammatory bowel disease. How luminal antigens cross the intestinal epithelium to interact with the immune system in a manner capable of induction and maintenance of oral tolerance is unknown. We have identified a new pathway of luminal antigen delivery to dendritic cells (DC) in the lamina propria (LP), which was mediated by goblet cells (GC) associated antigen passages (GAPs). The role of GCs and GAPs in promoting mucosal tolerance is unexplored. Methods: Tolerogenic responses to dietary antigen, ovalbumin (Ova) were studied in mice where GCs were deleted, or when GAPs are inhibited but GCs remain and compared to corresponding control mice. In addition, detailed analysis of DCs and T cell subsets within the lamina propria (LP) was performed upon deletion of intestinal GCs/GAPs or inhibition of GAPs. Results: Deletion of GCs or inhibition of GAPs prevented acquisition of luminal antigen by LP-DCs in a manner capable of inducing antigen specific T cell responses in the draining lymph nodes were abrogated. Moreover, inhibition of GAPs resulted in loss of induced Treg population in the small intestine and a loss of aldehyde dehydrogenase activity, the enzyme necessary for the production of all-trans retinoic acid, in LP CD103+ DCs. In addition, loss of GCs or inhibition of GAPs resulted in rapid expansion of IL-17 producing T cells in the small intestine, indicating that GCs and GAPs play a crucial role in balancing the Treg/Th-17 axis in the intestinal. Conclusion: These findings demonstrate that GCs and GAPs play a crucial role in the induction and maintenance of oral tolerance. Further these observations indicate and GCs have a previously unappreciated role in maintaining the Treg/Th17 balance and that processes resulting in inadequate formation of GAPs may underlie the loss of tolerance to luminal antigens.