Final Progress Report

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

Lay Summary:

An increased secretion of the c-type lectin PAP/REG3β is linked to disease severity in Crohn’s Disease.  However, the usefulness of PAP/REG3β testing in predicting relapsing disease and the mechanisms whereby PAP/REG3β is involved in intestinal homeostasis remain elusive.  Here, we describe a novel regulatory function for PAP/REG3β in the gut-microbiota dialogue.  Our 12-month prospective clinical study revealed that PAP/REG3β is not a predictive marker of clinical relapse.  However, the serological level of PAP/REG3β is linked to disease activity in Crohn’s disease, but not in ulcerative colitis.  Importantly, the level of fecal PAP/REG3β was markedly reduced in ulcerative colitis when compared to that in Crohn’s disease, suggesting a differential pathophysiological role of PAP/REG3β in Inflammatory Bowel Diseases.  To formally decipher the physiological role of PAP/REG3β in the colon, we used a transgenic mouse model of PAP/REG3β deficiency.  We concluded that PAP/REG3β function as a negative regulator of carcinogenesis and mucosal wound healing by licensing neutrophil-associated tissue damage and fecal microbial.  Development of drugs boosting PAP/REG3β function may thereby protect IBD patients' colons from clinical relapse and cancer development.