荷兰皇家艺术与科学院Hans Clevers小组取得一项新突破。他们的研究发现人肠道M细胞类似树突状细胞，呈现谷蛋白抗原。2025年12月10日，国际知名学术期刊《自然》发表了这一成果。

本文建立肠道类器官模型，研究人类M细胞，并通过转录组分析重建M细胞的分化轨迹。结果表明，除了促进腔内抗原转运外，人M细胞还通过II类主要组织相容性复合体（MHC-II）直接呈递抗原。值得注意的是，相关肠细胞仅在慢性炎症状态下表达MHC-II，而不表达典型的树突状细胞标记物。人类M细胞在生理上表达一种类似树突状细胞的基因谱。与树突状细胞类似，M细胞的发育由RANKL和CSF2诱导，并需要转录因子SPIB和RUNX2。HLA-DQ2.5 M细胞在类器官- t细胞共培养实验中加工和呈递谷蛋白抗原。这些发现表明M细胞可能在乳糜泻中起核心作用。

据介绍，微褶(M)细胞是一种罕见的肠上皮细胞，存在于Peyer's斑块的滤泡相关上皮中。M细胞将腔内抗原转运到粘膜下抗原呈递细胞。这些见解主要来自透射电子显微镜和对转基因小鼠主题的研究。

附：英文原文

Title: Human gut M cells resemble dendritic cells and present gluten antigen

Author: Wang, Daisong, Lim, Sangho, van de Wetering, Willine J., Lopez-Iglesias, Carmen, Okura, Yuu, Teranishi-Ikawa, Yuri, Mizoroki, Akihiko, Spoelstra, Willem Kasper, Dayton, Talya, van Son, Gijs J. F., Pronk, Apollo, Smakman, Niels, Gonera-de Jong, Gieneke B. C., Withoff, Sebo, Jonkers, Iris H., van Zon, Jeroen S., Tans, Sander J., Peters, Peter J., van Es, Johan H., Clevers, Hans

Issue&Volume: 2025-12-10

Abstract: Microfold (M) cells are rare intestinal epithelial cells that reside in the follicle-associated epithelium of Peyer’s patches1. M cells transport luminal antigens to submucosal antigen-presenting cells2,3. These insights primarily derive from transmission electron microscopy and studies using genetically modified mice2,3,4. Here we establish an intestinal organoid model to study human M cells and reconstruct the differentiation trajectory of M cells through transcriptome profiling. The results indicate that as well as facilitating luminal antigen transport, human M cells also directly present antigens via the class II major histocompatibility complex (MHC-II). Notably, the related enterocytes only express MHC-II in chronic inflammatory states and do not express typical dendritic cell markers. Human M cells physiologically express a gene profile that resembles that of dendritic cells. Similar to dendritic cells, M cell development is induced by RANKL and CSF2 and requires the transcription factors SPIB and RUNX2. HLA-DQ2.5 M cells process and present gluten antigen as demonstrated in organoid–T cell co-culture assays. These findings suggest that M cells may have a central role in coeliac disease.

DOI: 10.1038/s41586-025-09829-8

Source: https://www.nature.com/articles/s41586-025-09829-8