Genetic variation in NOD2 is associated with susceptibility to Crohn’s disease (CD), especially with ileal involvement.
However, the reason for this association of NOD2 mutations with ileal disease is unclear.
|Minimal NOD2 was detected in the villous epithelium of the ileum.|
In this study, researchers from the United States assessed the expression of NOD2 in intestinal tissue of CD patients and controls.
The team evaluated 55 specimens from 21 CD patients, 7 ulcerative colitis (UC) patients and 5 controls. Specimens were stained for NOD2 using an immunoperoxidase method.
Using a monoclonal antibody against NOD2, the team detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients. Uniform expression of NOD2 was also detected in metaplastic Paneth cells in the colon.
Using mechanical purification the researchers were able to show enriched expression of NOD2 mRNA in ileal crypts.
In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides.
The team detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls.
Dr Ogura's team concluded, "These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease".
"The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes".