Interleukin-4 suppresses the proliferation and alters the gene expression in enteroids
Interleukin-4 suppresses the proliferation and alters the gene expression in enteroids
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DOI：
10.1007/s10616-020-00395-7
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发表时间：
2020-04-23
期刊：
影响因子：
2.2
通讯作者：
Kobayashi-Hattori, Kazuo
中科院分区：
文献类型：
--
作者：
Saito, Yuki;Iwatsuki, Ken;Kobayashi-Hattori, Kazuo
白细胞介素(IL)-4被认为是一种主要参与过敏和炎症的细胞因子，但最近的研究表明，IL-4在多种细胞的分化过程中发挥作用。由于IL-4对肠上皮细胞，特别是包括干细胞在内的隐细胞的影响尚不清楚，我们利用小鼠空肠类器官（enteroid）研究了IL-4诱导的肠上皮细胞变化。IL-4处理降低了细胞增殖、干细胞标记物富亮氨酸重复-含G蛋白偶联受体5 （Lgr5）和olfactomedin 4 （Olfm4）的表达以及肠内Lgr5阳性细胞的表达。在分化标志物中，IL-4显著降低了Paneth细胞标志物溶菌酶1 （Lyz1）和再生胰岛源蛋白3 γ (Reg3 γ)的基因表达水平。荧光免疫染色显示，IL-4减弱了溶菌酶的发射和荧光强度，在Paneth细胞中富集。这些结果表明，IL-4引起的Paneth细胞功能改变可能有助于lgr5阳性细胞的减少和增殖活性的降低。IL-4可能通过改变肠样细胞的增殖和基因表达来影响肠道功能。
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 (Reg3 gamma). 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.