WSX-1: A key role in induction of chronic intestinal nematode infection
WSX-1: A key role in induction of chronic intestinal nematode infection
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DOI：
10.4049/jimmunol.172.12.7635
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发表时间：
2004-06-15
影响因子：
4.4
通讯作者：
Grencis, RK
中科院分区：
文献类型：
--
作者：
Bancroft, AJ;Humphreys, NE;Grencis, RK
在易感的AKR小鼠中，胃肠道线虫小鼠鞭虫的慢性感染与盲肠中IL-27 p28的表达相关，该小鼠产生Th 1应答。与野生型小鼠相比，缺乏WSX-1/IL-27 R基因的小鼠不能携带慢性感染，Th 1应答显着降低。发现WSX-1敲除（KO）小鼠中Ag特异性IFN-γ阳性细胞的较低水平是CD 4（+）T细胞特异性的，并且KO小鼠也具有IL-4阳性CD 4（+）T细胞的增加水平。来自初始WSX-1 KO或野生型小鼠的肠系膜淋巴结细胞的多克隆活化证明，CD 4（+）T细胞产生IFN-γ没有固有缺陷，这表明在感染的WSX-1 KO小鼠中观察到的这些细胞的减少是体内Ag驱动的效应。WSX-1 KO小鼠的IL-12治疗未能挽救I型应答，导致未改变的2型驱动的抗性。WSX-1 KO小鼠的感染也与盲肠内IL-27/WSX-1下游信号传导基因表达的减少相关。这些研究表明WSX-1信号在促进I型反应和慢性胃肠道线虫感染中的重要作用。
Chronic infection by the gastrointestinal nematode Trichuris muris in susceptible AKR mice, which mount a Th1 response, is associated with IL-27p28 expression in the cecum. In contrast to wild-type mice, mice that lack the WSX-1/IL-27R gene fail to harbor a chronic infection, having significantly lower Th1 responses. The lower level of Ag-specific IFN-gamma-positive cells in WSX-1 knockout (KO) mice was found to be CD4(+) T cell specific, and the KO mice also had increased levels of IL-4-positive CD4(+) T cells. Polyclonal activation of mesenteric lymph node cells from naive WSX-1 KO or wild-type mice demonstrated that there was no inherent defect in the production of IFN-gamma by CD4(+) T cells, suggesting the decrease in these cells seen in infected WSX-1 KO mice is an in vivo Ag-driven effect. IL-12 treatment of WSX-1 KO mice failed to rescue the type I response, resulting in unaltered type-2-driven resistance. Infection of WSX-1 KO mice was also associated with a reduction of IL-27/WSX-1 downstream signaling gene expression within the cecum. These studies demonstrate an important role for WSX-1 signaling in the promotion of type I responses and chronic gastrointestinal nematode infection.