The membrane-bound mucin Muc1 regulates T helper 17-cell responses and colitis in mice.
The membrane-bound mucin Muc1 regulates T helper 17-cell responses and colitis in mice.
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DOI：
10.1053/j.gastro.2011.12.036
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发表时间：
2012-04
期刊：
影响因子：
29.4
通讯作者：
Mizoguchi A
中科院分区：
文献类型：
--
作者：
Nishida A;Lau CW;Zhang M;Andoh A;Shi HN;Mizoguchi E;Mizoguchi A
辅助性T细胞（Th） 17产生效应细胞因子白细胞介素(IL)-17和IL-22，刺激结肠上皮细胞产生膜结合粘蛋白Muc1。Muc1是结肠黏液的一种成分，起润滑剂和管腔内容物与粘膜表面之间的生理屏障的作用。MUC1基因与炎症性肠病易感性相关；我们研究了Muc1在小鼠结肠炎发生中的作用。Muc1和RAG1在小鼠（Muc/RAG双敲除小鼠）中被破坏；通过静脉注射CD4+CD45RBhigh T细胞诱导th1介导的结肠炎。我们还使用Muc1和t细胞受体α链被破坏的小鼠（Muc/TCR双敲除小鼠）研究了th2介导的结肠炎。Muc1缺乏导致Th1-和th2诱导的结肠炎比对照组更严重。Muc1的缺失增加了结肠通透性和th17细胞，而不是Th2或Th1细胞对炎症结肠的反应。Muc1的缺失也促进了产生IL-17的先天淋巴样细胞群（Lin - ckit - Thy1+ Sca1+）的扩增。Th17适应性免疫细胞和先天淋巴样细胞的扩增需要共生菌群。Muc1被Th17信号上调，在小鼠炎症结肠中发挥负反馈作用，防止Th17细胞过度反应。这种负反馈通路的破坏，可能是Muc1的变异，可能导致患者的炎症性肠病。
T helper (Th) 17 cells produce the effector cytokine interleukin (IL)-17, along with IL-22, which stimulates colonic epithelial cells to produce a membrane-bound mucin, Muc1. Muc1 is a component of the colonic mucus, which functions as a lubricant and a physiologic barrier between luminal contents and mucosal surface. The gene MUC1 has been associated with susceptibility to inflammatory bowel disease; we investigated the role of Muc1 in development of colitis in mice. Muc1 and RAG1 were disrupted in mice (Muc/RAG double knockout mice); Th1-mediated colitis was induced by intravenous injection of CD4+CD45RBhigh T cells. We also studied Th2-mediated colitis using mice with disruptions in Muc1 and T-cell receptor α chain (Muc/TCR double knockout mice). Muc1 deficiency led to the development of more severe forms of Th1- and Th2-induced colitis than controls. Loss of Muc1 increased colonic permeability and the Th17-cell, but not Th2 or Th1 cell, response in the inflamed colon. Loss of Muc1 also promoted expansion of an innate lymphoid cell population (Lin− ckit− Thy1+ Sca1+) that produces IL-17. The expansion of Th17 adaptive immune cells and innate lymphoid cells required the commensal microbiota. Muc1, which is up-regulated by Th17 signaling, functions in a negative feedback pathway that prevents an excessive Th17 cell response in inflamed colons of mice. Disruption of this negative feedback pathway, perhaps by variants in Muc1, might contribute to inflammatory bowel disease in patients.
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.4
作者：
Andoh, Akira;Shioya, Makoto;Fujiyama, Yoshihide
通讯作者：
Fujiyama, Yoshihide
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.
DOI：
10.1084/jem.20101330
发表时间：
2010-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Asquith M;Powrie F
通讯作者：
Powrie F