Lay Summary

Proposal No.  IBD-0007
Principal Investigator:  Johan D. Söderholm, M.D., Ph.D.
Applicant Organization: Linköping University (Sweden)
Project Title:  The role of the follicle-associated epithelium in the initiation of inflammatory bowel disease
Period of Award:  November 1, 2002 – September 30, 2005

Inflammatory bowel disease represents the outcome of the interaction between the predisposition of the host (genetic and environmental), the local mucosal immune response, and the bacterial flora in the intestinal lumen.  The earliest observable lesions in Crohn’s disease are microscopic erosions in the specialized intestinal lining covering areas of organized mucosal immune cells.  At these sites, the intestinal lining contains the so-called M cells, which are specialized for sampling of foreign material from the intestinal lumen.  This is believed to be crucial for induction of protective mucosal immune responses, but also provides a route of entry into the body for various infectious or immunogenic agents.

Our hypothesis is that a malfunction in the interaction between luminal agents, intestinal cells, and immune cells that takes place at these sites is a crucial step in the initiation of mucosal inflammation in Crohn’s disease.

We will do the first functional characterization in the human intestine of these specialized areas of intestinal lining.  We will also be able to compare the mucosal defense against invasion of luminal bacteria in Crohn’s disease and control patients.  Thereby, the project will be the first to study the actual process of bacterial uptake into the mucosa in inflammatory bowel disease and will add important insights into what is thought to be a crucial step in the development of intestinal inflammation.

This project will provide novel information on the cause and development of Crohn’s disease and thereby give important clues for new treatments or a cure for this debilitating condition.