Final Progress Report

Proposal No. IBD-0007
Principal Investigator:  Johan 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

Lay summary:

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 ulcers in the specialized intestinal lining covering areas of organized immune cells. At these sites, sampling of foreign material from the intestinal lumen takes place. This is believed to be crucial for protective mucosal immune responses, but is also used as a route of entry into the body for various infectious agents.

Our hypothesis in the present project was that a malfunction in the interaction between luminal infectious 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.

In studies of diseases with unknown etiology, it is pertinent to do studies in patients and patient tissue since the various models of the disease will only be approximations. Within the project we have established techniques for studies of the specialized, so-called follicle-associated, regions of the intestinal lining in humans. We have been able to compare the mucosal defense against invasion of luminal bacteria in patients with Crohn’s disease and control patients. Moreover, we have begun to study the role of the so-called dendritic cells, which are important cells in the first line of immune defense.

So far, we have four papers published through funding from the Broad Foundation, and three papers submitted. Moreover, we have been able to acquire funding from the Swedish Research Council – Medicine for a continuation and expansion of the project with an amount almost twice the average funding from the SRC.

We will continue this line of research and anticipate providing novel data on the interaction of the intestinal mucosa with the gut flora during inflammation. We will thereby continue to increase the understanding of crucial steps in the pathogenesis of IBD and disease relapse, ultimately leading to novel therapeutic approaches for these debilitating diseases.