NOD2 Role in Post-Operative Ileal Recurrence during the Crohn's Disease: Study on Genetically Engineered Mice Model

The presence of NOD2 mutation is associated with an increased use of surgery and decreased recurrence-free interval in Crohn's disease, suggesting a strong link between NOD2 and development of intestinal inflammation. The aim of the study was to determine whether a NOD2 mutation could lead worsening inflammatory phenomena by developing two protocols inducing ileal inflammation on a mouse model with 1007fs NOD2 mutation: a surgical protocol and inflammation radio induced.In the surgical model, a mouse 1007fs group and a control group Wild Type (WT) underwent ileocecal resection. The ileocolic anastomosis area was removed at 4 or 6 weeks for histologic analysis and analysis of the expression of proinflammatory cytokines. In the radiation model, an ileal loop was irradiated in two groups of mice: WT and 1007fs, with two doses: 13Gy and 16Gy. These segments were taken at 7 and 21 days for histological analysis.In the surgical model, ileal inflammation appeared greater among 1007fs but no significant difference in the expression of pro-inflammatory cytokines was observed. In the radiation model, histological analysis revealed significantly greater inflammation at 7 days in 1007fs with 13Gy but not with 16 Gy (p = 0.01 and p = 0.68 respectively). This difference was no longer significant at 21 days.Our results suggest that a mutation disabling the function of NOD2 increases the ileal sensitivity in two complementary experimental models of inflammation induced.