T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis.

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 beta2 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-gamma, IL-6, and tumor necrosis factor-alpha 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.

An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis.

Evidence suggests that CD4+CD25+ regulatory T cells play a crucial role in the suppression of intestinal inflammation. However, their role in the suppression of inflammatory bowel disease has not yet been addressed. We examined the proportion of regulatory T cells in inflammatory bowel disease. First, we isolated CD4+CD45RO+CD25+ T cells from the peripheral blood of healthy persons and showed that these cells suppressed T cell proliferation profoundly and expressed FoxP3 abundantly, revealing that they are regulatory cells. Then the proportion of CD45RO+CD25+ in peripheral blood CD4+ T cells was analyzed in patients and healthy controls by flow cytometry. CD4+CD45RO+CD25+ T cell frequency was significantly lower in active ulcerative colitis than in the control and inactive ulcerative colitis. CD4+CD45RO+CD25+ T cell frequency was inversely correlated with the clinical and endoscopic severity of ulcerative colitis. These results suggest that a deficiency of regulatory T cells is associated with the progression of ulcerative colitis.