T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis
T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis
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DOI：
10.1097/01.mib.0000191611.05466.1f
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发表时间：
2005-12-01
影响因子：
4.9
通讯作者：
Yoshida, H
中科院分区：
文献类型：
--
作者：
Honda, K;Nakamura, K;Yoshida, H
背景资料：WSX-1是白细胞介素（IL）-27受体的一个组分，是一种与IL-12受体132链具有同源性的新型I类细胞因子受体。最初，WSX-1信号被报道在促进T辅助细胞-1应答中起重要作用，但最近的报道揭示了WSX-1信号的抗炎特性。本研究采用WSX-1基因敲除（KO）小鼠，观察IL-27/WSX-1信号通路在小鼠结肠炎模型dexn-an sulfate sodium（DSS）colitis中的作用。第二，我们在WSX-1 KO和野生型（WT）小鼠中诱导DSS结肠炎。与WT小鼠相比，WSX-1 KO小鼠中DSS结肠炎的严重程度降低，这与来自WSX-1 KO小鼠的固有层单核细胞产生的干扰素-γ、IL-6和肿瘤坏死因子-α的减少以及来自WSX-1 KO小鼠的结肠中T-bet表达的缺乏有关。本研究揭示了IL-27/WSX-1信号在肠道炎症中的炎症特性。结果。因此，IL 27/WSX-1信号通路可能是一个有前途的候选人，为人类炎症性肠病，如克罗恩病和溃疡性结肠炎的治疗干预。
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 132 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, dexn-an 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. IL27/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.