Interleukin (IL)-4 is known as a cytokine mainly involved in allergy and inflammation, but recent studies have suggested that IL-4 plays a part in the differentiation process of various cells. Since the effect of IL-4 on intestinal epithelial cells, particularly cryptic cells including stem cells, is poorly understood, we investigated IL-4-induced changes in intestinal epithelial cells using mouse jejunal organoids called enteroids. IL-4 treatment decreased cell proliferation, the expression of the stem cell markers leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and olfactomedin 4 (Olfm4), and Lgr5-positive cells in enteroids. Among the differentiation markers, IL-4 significantly decreased the gene expression levels of the Paneth cell markers lysozyme 1 (Lyz1) and regenerating islet-derived protein 3 gamma (Reg3γ). A fluorescent immunostaining showed that IL-4 attenuated the emission and fluorescence intensity derived from lysozyme, which is enriched in Paneth cells. These results suggest that functional changes in Paneth cells caused by IL-4 may contribute to the reduction in Lgr5-positive cells and proliferative activity. IL-4 may affects gut function by altering the proliferation and the gene expression in enteroids.

中文翻译：

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白介素-4抑制增殖并改变小肠中的基因表达。

白介素（IL）-4被称为主要参与变态反应和炎症的细胞因子，但最近的研究表明IL-4在各种细胞的分化过程中发挥了作用。由于对IL-4对肠上皮细胞（特别是包括干细胞在内的隐性细胞）的作用了解甚少，因此我们使用称为肠样的小鼠空肠类器官研究了IL-4诱导的肠上皮细胞的变化。IL-4处理降低了细胞增殖，降低了富含亮氨酸重复序列的G蛋白偶联受体5（Lgr5）和olfactomedin 4（Olfm4）的干细胞标记以及Lgr5阳性细胞在小肠中的表达。在分化标记中，IL-4显着降低了Paneth细胞标记溶菌酶1（Lyz1）的基因表达水平，并再生了胰岛衍生蛋白3γ（Reg3γ）。荧光免疫染色显示IL-4减弱了溶菌酶的发射和荧光强度，溶菌酶富含Paneth细胞。这些结果表明由IL-4引起的Paneth细胞的功能变化可能有助于Lgr5阳性细胞的减少和增殖活性。IL-4可能通过改变小肠的增殖和基因表达来影响肠道功能。