Background: Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are characterized by recurrent inflammation in the gastrointestinal tract. Infiltration of CD4 lymphocytes and neutrophils is one of the predominant features of IBD.
Materials and methods: Recently, interleukin (IL)-23 and the downstream T cell-derived cytokine IL-17 have been found to be elevated in intestinal tissue and serum of IBD patients. However, the role of IL-17 and IL-17R signaling in gut inflammation is unknown. To examine this role, we investigated gut inflammation in wild-type or IL-17R knockout mice.
Results: Using a model of acute trinitrobenzenesulfonic acid (TNBS)-induced colitis, we found that IL-17 was produced in colon tissue at 24 and 48 hours and that IL-17R knockout mice were significantly protected against TNBS-induced weight loss, IL-6 production, colonic inflammation, and local macrophage inflammatory protein-2 induction. This protection occurred in the presence of equivalent induction of local IL-23 and higher levels of IL-12p70 and interferon-gamma in IL-17R knockout mice compared with wild-type mice. Moreover, IL-17R knockout mice showed reduced tissue myeloperoxidase activity. Furthermore, overexpression of an IL-17R IgG1 fusion protein significantly attenuated colonic inflammation after acute TNBS.
Conclusions: These results demonstrate that IL-17R signaling plays a critical role in the development of TNBS-induced colitis and may represent a target for therapeutic intervention for IBD.