Gastroenterology:维甲酸和淋巴毒素信号可以促进人类肠道M细胞的分化

2020-04-11 MedSci原创 MedSci原创

肠道微折叠(M)细胞是Peyer斑中肠道上皮细胞的独特亚型细胞,可调节粘膜免疫力,还可作为腔内抗原采样和摄取的第一道防线。但是目前的技术无法在细胞培养中有效培育人类M细胞。

背景与目标:肠道微折叠(M)细胞是Peyer斑中肠道上皮细胞的独特亚型细胞,可调节粘膜免疫力,还可作为腔内抗原采样和摄取的第一道防线。但是目前的技术无法在细胞培养中有效培育人类M细胞,这阻碍了肠道免疫系统的研究。因此,本项研究旨在鉴定人类M细胞分化所需的信号通路,并建立使用人类回肠肠样物质的稳健培养系统。

方法:研究人员分析了来自小鼠Peyer's Patches的转录组数据,以鉴定紧邻M细胞的细胞群体,并使用人类肠样系统来确定诱导M细胞分化所需的细胞因子。最后进行了转录组,免疫荧光,扫描电子显微镜和转胞吞实验,以验证表型和功能性人类M细胞的发育所需物。

结果:本项研究发现视黄酸和淋巴毒素的组合可诱导糖蛋白2阳性的人类M细胞分化,而后者缺乏顶微绒毛结构。轮状病毒感染后,M细胞中先天性免疫相关基因的表达上调与缺乏病毒抗原有关。在肠样系统中发育的人类M细胞将肠道病毒(如轮状病毒和呼肠孤病毒)内化和转运,穿过肠样物中的肠上皮屏障。

结论:本项研究确定了肠道M细胞分化所需的信号通路,并使用此信息创建了一种强大的培养方法来开发具有病毒内在化和运输能力的人M细胞。

原始出处:

Siyuan Ding. Et al. Retinoic Acid and Lymphotoxin Signaling Promote Differentiation of Human Intestinal M Cells. Gastroenterology.2020.

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    2020-07-19 许安
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