IFN-γ-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia.
IFN-γ-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia.
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DOI：
10.4049/jimmunol.1301757
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发表时间：
2014-02-01
期刊：
影响因子：
--
通讯作者：
Bruder D
中科院分区：
文献类型：
--
作者：
Kominsky DJ;Campbell EL;Ehrentraut SF;Wilson KE;Kelly CJ;Glover LE;Collins CB;Bayless AJ;Saeedi B;Dobrinskikh E;Bowers BE;MacManus CF;Müller W;Colgan SP;Bruder D
在炎症部位分泌的细胞因子影响炎症的发作、进展和消退。在此，我们研究了IFN-γ在炎症性肠病（IBD）模型中的潜在促消退机制。在最初的微阵列分析的指导下，体外研究显示IFN-γ选择性地诱导肠上皮细胞上IL-10 R1的表达。进一步的分析表明，IL-10 R1主要表达在极化上皮细胞的顶膜上。受体激活功能性诱导上皮细胞中典型IL-10靶基因表达，同时增强屏障恢复。此外，肠上皮细胞中IL-10 R1的敲低导致体外屏障功能受损。从鼠结肠炎分离的结肠组织显示，上皮中IL-10 R1和SOCS 3的水平增加，并且与组织IFN-γ和IL-10细胞因子的增加一致。同时，研究表明，用rIFN-γ处理小鼠足以驱动结肠上皮中IL-10 R1的表达。在肠上皮特异性IL-10 R1缺失小鼠中进行的DSS结肠炎研究显示，与肠通透性增加相关的疾病易感性显著增加。总之，这些结果为上皮IL-10信号传导在上皮屏障的维持和恢复以及IFN-γ对这些途径的时间调节中的关键和未被充分认识的作用提供了新的见解。
Cytokines secreted at sites of inflammation impact the onset, progression and resolution of inflammation. Here we investigated potential pro-resolving mechanisms of IFN-γ in models of inflammatory bowel disease (IBD). Guided by initial microarray analysis, in vitro studies revealed that IFN-γ selectively induced the expression of IL-10R1 on intestinal epithelia. Further analysis revealed that IL-10R1 was expressed predominantly on the apical membrane of polarized epithelial cells. Receptor activation functionally induced canonical IL-10 target gene expression in epithelia, concomitant with enhanced barrier restitution. Furthermore, knockdown of IL-10R1 in intestinal epithelial cells results in impaired barrier function in vitro. Colonic tissue isolated from murine colitis revealed that levels of IL-10R1 and SOCS3 were increased in the epithelium and coincided with increased tissue IFN-γ and IL-10 cytokines. In parallel, studies showed that treatment of mice with rIFN-γ was sufficient to drive expression of IL-10R1 in the colonic epithelium. Studies of DSS colitis in intestinal epithelial-specific IL-10R1-null mice revealed a remarkable increase in disease susceptibility associated with increased intestinal permeability. Together, these results provide novel insight into the crucial and underappreciated role of epithelial IL-10 signaling in the maintenance and restitution of epithelial barrier and of the temporal regulation of these pathways by IFN-γ.
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DOI：
10.4049/jimmunol.1001442
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Glover LE;Irizarry K;Scully M;Campbell EL;Bowers BE;Aherne CM;Kominsky DJ;MacManus CF;Colgan SP
通讯作者：
Colgan SP
影响因子：
29.4
作者：
Gurtner, GJ;Newberry, RD;Stenson, WF
通讯作者：
Stenson, WF
影响因子：
15.9
作者：
Khoury, Joseph;Ibla, Juan C.;Colgan, Sean R.
通讯作者：
Colgan, Sean R.
DOI：
10.4049/jimmunol.1002805
发表时间：
2011-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kominsky DJ;Keely S;MacManus CF;Glover LE;Scully M;Collins CB;Bowers BE;Campbell EL;Colgan SP
通讯作者：
Colgan SP
影响因子：
5.5
作者：
Kelchtermans, Hilde;Struyf, Sofie;Matthys, Patrick
通讯作者：
Matthys, Patrick