Lay Summary

Proposal No. IBD-0222R
Principal Investigator:  Mathias Chamaillard, Ph.D.
Applicant Organization:  Institut Pasteur de Lille (France)
Project Title:  Role of a c-type lectin on NOD2 signaling in Crohn's disease
Period of Award:  April 1, 2008 – February 28, 2011

Inflammatory bowel disease (IBD) is a widespread and increasingly common and chronic intestinal illness, affecting millions worldwide.  The treatment of IBD is, at present, far from optimal. Therefore, there is clearly a need to identify alternative therapies and develop non-invasive biomarkers capable of predicting relapsing disease.

IBD might result from an overly aggressive immune response to microbial antigens in genetically-predisposed individuals. Notably, about a third of CD patients are mutated for a gene encoding a ‘sensor’ of invading microbes, namely NOD2. However, the multiple pathophysiological processing steps linking environmental exposure to the clinical expression of IBD are, for the most part, unpredictable. In IBD, others and we recently reported increased expression levels of the microbially-induced c-type lectin PAP, which control bacterial proliferation and host tissue repair. Accordingly, PAP-deficient mice were protected against IBD, suggesting a detrimental role for PAP in IBD pathogenesis.

The aims of the project are to i) determine the clinical value of PAP testing in predicting clinical relapse in IBD patients and ii) determine the physiological role of PAP in maintaining intestinal barrier integrity through NOD2. In the near future, our proposed studies might help the physicians to choose the optimal therapeutic strategy for each individual patient with a simple laboratory test, as well as crucial clues to the development of alternative prophylactic therapies aimed at blocking PAP.