Immune regulatory mechanism in mouse IBD model (168.26)

Abstract

Inflammatory bowel disease (IBD) in humans, such as Crohn’s disease and ulcerative colitis, is characterized by chronic inflammation with dysregulated mucosal immune tolerance. Some reported that immune responses to intestinal microbiota are critical to develop IBD and NOD-like receptor-mediated inflammasome is related to epithelial integrity. In order to investigate dysregulated mechanism focusing on the relationship between inflammasome and regulatory cells in IBD, we used a 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in WT-C57BL/6 mice and caspase-1-/- mice. In addition, to observe Th2-dependent immune responses in IBD mouse, we also used WT-Balb/c mice and eosinophil-deficient ΔdblGATA mice. As a result, mice treated TNBS had significant changes in clinical parameters, weight loss, and colonic weights compared with those of sham control mice. Histologic analysis also showed severe inflammation in intestines of TNBS treated mice. We found that deficiency of eosinophil or IL-1β had resistance in initial stage of disease progression, represented by survival score and body weight loss and we also noted that proportion of Foxp3+ cells and myeloid-derived suppressor cells (MDSCs) increased in above TNBS-treated ΔdblGATA and caspase-1-/- mice. These results provide us another mechanism of immune modulation in the pathogenesis of intestinal inflammation.