Epithelium-Intrinsic MicroRNAs Contribute to Mucosal Immune Homeostasis by Promoting M-Cell Maturation.
Epithelium-Intrinsic MicroRNAs Contribute to Mucosal Immune Homeostasis by Promoting M-Cell Maturation.
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DOI：
10.1371/journal.pone.0150379
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Ohno H
中科院分区：
文献类型：
--
作者：
Nakato G;Hase K;Sato T;Kimura S;Sakakibara S;Sugiyama M;Obata Y;Hanazato M;Iwanaga T;Ohno H
派尔集合淋巴结（Peyer’s patches，PP）滤泡相关上皮（FAE）中的M细胞是外部抗原的主要入口，并在粘膜免疫应答中起前哨作用。这些细胞的缺乏阻碍了M细胞特异性分子的鉴定。最近的努力已经开始提供深入了解抗原转胞吞作用和M细胞的分化，然而，这些过程的分子机制尚未完全阐明。包括microRNA（miRNA）在内的小分子非编码RNA已被报道调节基因表达并控制各种生物学过程，如细胞分化和功能。为了评估FAE（包括M细胞）中miRNA的表达，我们之前进行了微阵列分析，比较了肠绒毛上皮（VE）和PP FAE。在这里，我们通过定量PCR证实了FAE特异性miRNA的表达水平。为了深入了解miRNA的功能，我们产生了肠上皮细胞特异性缺失Dicer 1（DicerΔIEC）的小鼠，并分析了肠道表型，包括M细胞分化，形态和功能。与对照floxed Dicer小鼠相比，DicerΔIEC小鼠的M细胞显著减少，表明miRNA在这些细胞的成熟中起重要作用。此外，透射电子显微镜分析显示，在M细胞中，miRNA的耗尽导致内体结构的丢失。此外，DicerΔIEC小鼠中M细胞的抗原摄取受损。这些结果表明，miRNA在M细胞分化中起重要作用，并有助于确保粘膜免疫稳态。
M cells in the follicle-associated epithelium (FAE) of Peyer’s patches (PPs) serve as a main portal for external antigens and function as a sentinel in mucosal immune responses. The scarcity of these cells has hampered identification of M cell-specific molecules. Recent efforts have begun to provide insight into antigen transcytosis and differentiation of M cells; however, the molecular mechanisms underlying these processes are not fully elucidated. Small non-coding RNAs including microRNA (miRNA) have been reported to regulate gene expression and control various biological processes such as cellular differentiation and function. To evaluate the expression of miRNAs in FAE, including M cells, we previously performed microarray analysis comparing intestinal villous epithelium (VE) and PP FAE. Here we confirmed FAE specific miRNA expression levels by quantitative PCR. To gain insight into miRNA function, we generated mice with intestinal epithelial cell-specific deletion of Dicer1 (DicerΔIEC) and analyzed intestinal phenotypes, including M-cell differentiation, morphology and function. DicerΔIEC mice had a marked decrease in M cells compared to control floxed Dicer mice, suggesting an essential role of miRNAs in maturation of these cells. Furthermore, transmission electron microscopic analysis revealed that depletion of miRNA caused the loss of endosomal structures in M cells. In addition, antigen uptake by M cells was impaired in DicerΔIEC mice. These results suggest that miRNAs play a significant role in M cell differentiation and help secure mucosal immune homeostasis.