Final Progress Report

Proposal No.   IBD-0091R
Principal Investigator:  Gabriel Nuñez, M.D.
Applicant Organization:  University of Michigan (Ann Arbor, U.S.A.)
Project Title:  Role of Nod2 in the control of Paneth cell function and intestinal microflora 
Period of Award:  May 1, 2004 - May 31, 2006

Lay abstract

Crohn’s disease (CD) is a chronic and debilitating disease affecting more than 500,000 individuals in the United States and millions worldwide.   Both environmental (particularly intestinal bacteria) and genetic factors are known to play a critical role in the development of CD.  Recent studies have revealed that faulty versions of the gene NOD2 are carried by some individuals which make them more susceptible to CD. The normal NOD2 gene is thought to be part of a defense mechanism against certain bacteria in the gut tissue.  Faulty NOD2 mutations result in defective recognition of bacteria which may cause inflammation in the gut by a mechanism that  remains poorly understood.   Surprisingly, we find that NOD2 is expressed in Paneth cells that are specialized intestinal cells located at the base of the cellular lining of the small intestine, a site frequently involved in disease.  Paneth cells secrete molecules against bacteria and appear to be involved in the defense against intestinal bacteria.  Our studies revealed that NOD2 functions in the gut to control infection by some intestinal microbes. The studies of the work also suggest that NOD2 functions at least in part by controlling the secretion of certain anti-microbial molecules produced by Paneth cells in the gut.