IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis
IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis
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DOI：
10.4161/21688370.2014.983777
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发表时间：
2015-01-01
期刊：
影响因子：
3.1
通讯作者：
Weigmann, Benno
中科院分区：
文献类型：
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作者：
Gerlach, Katharina;McKenzie, Andrew N.;Weigmann, Benno
由于以往的研究表明IL-9可能控制肠道屏障功能，我们测试了IL-9在半抗原试剂2,4,6三硝基苯磺酸（TNBS）诱导的实验性T细胞介导的结肠炎中的作用。IL-9缺乏可抑制tnbs诱导的结肠炎，导致PU数量减少。1在固有层表达T细胞，提示Th9细胞在实验性TNBS结肠炎模型中具有调节作用。由于已知IL-9在结肠炎症中功能性地改变肠屏障功能，我们评估了TNBSinflamed小鼠肠上皮细胞中紧密连接分子的表达。因此，我们对野生型和IL-9小鼠炎症结肠紧密连接分子进行实时PCR分析，免疫荧光染色，并通过Western blot直接研究tnbs -炎症小鼠肠上皮细胞中连接蛋白的表达。结果表明，闭塞蛋白（occludin）等封闭蛋白在炎症IL-9 KO小鼠的结肠中上调。而当IL-9缺失时，紧密连接蛋白Claudin1的表达水平较低。令人惊讶的是，形成孔的分子Claudin2在tnb处理的野生型和缺乏il -9的动物中表达相同。这些结果说明IL-9在实验性结肠炎中改变肠通透性的多效性功能。因此，调节IL-9功能成为调节肠道炎症屏障功能的新途径。
As previous studies suggested that IL-9 may control intestinal barrier function, we tested the role of IL-9 in experimental T cell-mediated colitis induced by the hapten reagent 2,4,6trinitrobenzenesulfonic acid (TNBS). The deficiency of IL-9 suppressed TNBS-induced colitis and led to lower numbers of PU. 1 expressing T cells in the lamia propria, suggesting a regulatory role for Th9 cells in the experimental TNBS colitis model. Since IL-9 is known to functionally alter intestinal barrier function in colonic inflammation, we assessed the expression of tight junction molecules in intestinal epithelial cells of TNBSinflamed mice. Therefore we made real-time PCR analyses for tight junction molecules in the inflamed colon from wild-type and IL-9 KO mice, immunofluorescent stainings and investigated the expression of junctional proteins directly in intestinal epithelial cells of TNBS-inflamed mice by Western blot studies. The results demonstrated that sealing proteins like occludin were up regulated in the colon of inflamed IL-9 KO mice. In contrast, the tight junction protein Claudin1 showed lower expression levels when IL-9 is absent. Surprisingly, the pore-forming molecule Claudin2 revealed equal expression in TNBStreated wild-type and IL-9-deficient animals. These results illustrate the pleiotropic functions of IL-9 in changing intestinal permeability in experimental colitis. Thus, modulation of IL-9 function emerges as a new approach for regulating barrier function in intestinal inflammation.