Conditional Epithelial Deletion of the Pathogen Recognition Receptor Nod2 Fails to Alter the Regulation of T cell-Induced Enteropathy

The pathogen recognition receptor Nod2 plays an important role in intestinal barrier maintenance and host defence against bacterial microbes. Inflammatory Bowel Diseases are thought to result from a loss of tolerance towards the normal intestinal microbiota due to an inappropriate and continuing inflammatory response and/or an unstable or leaky mucosal barrier. Loss-of-function mutations in the NOD2 gene are significantly associated with higher risks of developing Crohn's disease. We showed that acute T cell activation induced stronger damage in crypt architecture, epithelial apoptosis and delayed epithelial regeneration in NOD2^-/- mice. To assess the role of Nod2 function in epithelial cells versus T cells, we created a conditional deletion of Nod2 in the intestinal epithelium. Anti-CD3 induced enteropathy in NOD2^ΔIEC mice and mucosal healing was not different from that in WT mice. In contrast, transfer of Nod2 deficient CD4⁺ T cells into Rag1^-/- mice led to a dramatic mortality rate after in vivo T cell activation. Our results indicate that Nod2 is an important regulator of small intestine mucosal damage and its expression in CD4⁺ T cells is important to control the pathophysiological response to acute T cell activation in the gut.