Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum

• DOI: 10.1073/pnas.1003363107
• Publication Date: 2010-08-03T03:35:49Z
• Authors: Amlan Biswas; Yuen-Joyce Liu; Liming Hao; Atsushi Mizoguchi; Nita H. Salzman; Charles L. Bevins; Koichi S. Kobayashi
• Keywords: Paneth cell

Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn’s disease. However, mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy. We report that Nod2 -deficient mice inoculated with Helicobacter hepaticus , an opportunistic pathogenic bacterium, developed granulomatous ileum, characterized increased expression Th1-related genes and inflammatory cytokines. The Peyer’s patches mesenteric lymph nodes were markedly enlarged expansion IFN-γ–producing CD4 CD8 T cells. Rip2 exhibited similar phenotype, suggesting function likely depends on kinase this model. Transferring wild-type bone marrow cells into irradiated did not rescue phenotype. restoring crypt antimicrobial transgenic α-defensin Paneth rescued Th1 Therefore, through regulation microbes, nonhematopoietic small crypts is critical protecting from Th1-driven ileum. model may provide insight relevant