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Selective expression of constitutively activated STAT6 in intestinal epithelial cells promotes differentiation of secretory cells and protection against helminths.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-Nov-16 , DOI: 10.1038/s41385-018-0107-3
Christoph Schubart 1 , Branislav Krljanac 1 , Manuel Otte 1 , Cornelia Symowski 1 , Eva Martini 2 , Claudia Günther 2 , Christoph Becker 2 , Christoph Daniel 3 , David Voehringer 1
Affiliation  

Intestinal epithelial cells (IECs) constitute an important barrier between host and pathogen. Immune mechanisms that provide protection against gastrointestinal helminths often require IL-4Rα-induced activation of STAT6-regulated genes in IECs. However, it is not known whether STAT6 activation in IECs enhances protective immunity against helminths. Furthermore, the regulation of proliferation and differentiation processes of the intestinal epithelium by IEC-intrinsic STAT6 signaling remains unclear. To address these questions, we generated mice with specific expression of a constitutively active version of STAT6 in IECs. These VillinCre_STAT6vt mice show accumulation of secretory IECs, increased proliferation of IECs and lengthening of the small intestine. They rapidly expelled Nippostrongylus brasiliensis worms even in the absence of T cells. Furthermore, primary infection with Heligmosomoides polygyrus resulted in larval trapping in the submucosa and the fecundity of adult worms was severely impaired. Our results reveal an important IEC-intrinsic role of STAT6-regulated genes for intestinal homeostasis and protective immunity against helminths.

中文翻译:

组成型激活的 STAT6 在肠上皮细胞中的选择性表达促进分泌细胞的分化和对蠕虫的保护。

肠上皮细胞 (IEC) 构成宿主和病原体之间的重要屏障。提供针对胃肠道蠕虫保护的免疫机制通常需要 IL-4Rα 诱导 IEC 中 STAT6 调节基因的激活。然而,尚不清楚 IEC 中的 STAT6 激活是否增强了对蠕虫的保护性免疫力。此外,IEC 固有的 STAT6 信号转导对肠上皮增殖和分化过程的调节仍不清楚。为了解决这些问题,我们生成了在 IEC 中特异性表达 STAT6 组成型活性版本的小鼠。这些 VillinCre_STAT6vt 小鼠显示出分泌性 IEC 的积累、IEC 的增殖增加和小肠的延长。即使在没有 T 细胞的情况下,它们也能迅速驱除巴西尼波氏圆线虫。此外,Heligmosomoides polygyrus 的原发性感染导致幼虫被困在粘膜下层,成虫的繁殖力严重受损。我们的结果揭示了 STAT6 调节基因对肠道稳态和对蠕虫的保护性免疫的重要 IEC 内在作用。
更新日期:2019-01-26
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