T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis
Article first published online: 14 DEC 2006
Copyright © 2005 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 11, Issue 12, pages 1044–1052, December 2005
How to Cite
Honda, K., Nakamura, K., Matsui, N., Takahashi, M., Kitamura, Y., Mizutani, T., Harada, N., Nawata, H., Hamano, S. and Yoshida, H. (2005), T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis. Inflamm Bowel Dis, 11: 1044–1052. doi: 10.1097/01.MIB.0000191611.05466.1f
- Issue published online: 14 DEC 2006
- Article first published online: 14 DEC 2006
- Manuscript Accepted: 21 SEP 2005
- Manuscript Received: 26 APR 2004
- Ministry of Education, Science, Technology, Sports and Culture of Japan (H.Y.), from the Japan Research Foundation for Clinical Pharmacology (H.Y.), from the Sumitomo Foundation, Grant for Basic Science Research Projects (H.Y.), and from the Uehara Memorial Foundation (H.Y.)
- inflammatory bowel diseases;
- interleukin-27 receptor;
- dextran sulfate sodium;
Background: WSX-1, a component of the interleukin (IL)-27 receptor, is a novel class I cytokine receptor with homology to the IL-12 receptor β2 chain. Initially, WSX-1 signaling was reported to play an important role in the promotion of T helper-1 responses, but recent reports have revealed an anti-inflammatory property in WSX-1 signaling. In the present study, we investigated the role of IL-27/WSX-1 signaling in a murine colitis model, dextran sulfate sodium (DSS) colitis, by using WSX-1 knockout (KO) mice. Methods: First, we observed whether WSX-1 KO mice developed colitis spontaneously. Second, we induced DSS colitis in WSX-1 KO and wild-type (WT) mice. Results:WSX-1 KO mice were observed not to develop colitis spontaneously. The severity of DSS colitis was decreased in WSX-1 KO mice in comparison with WT mice in association with a reduced production of interferon-γ, IL-6, and tumor necrosis factor-α by lamina propria mononuclear cells from WSX-1 KO mice and the absence of T-bet expression in the colon from WSX-1 KO mice. Conclusions: This study revealed the inflammatory property of IL-27/WSX-1 signaling in intestinal inflammation. As a result, IL-27/WSX-1 signal pathway may thus be a promising candidate for the therapeutic intervention of human inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.