Peyer's Patch Dendritic Cells Sample Antigens by Extending Dendrites Through M Cell-Specific Transcellular Pores
Peyer's Patch Dendritic Cells Sample Antigens by Extending Dendrites Through M Cell-Specific Transcellular Pores
复制标题
DOI：
10.1053/j.gastro.2011.11.039
复制
发表时间：
2012-03-01
期刊：
影响因子：
29.4
通讯作者：
Gorvel, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Lelouard, Hugues;Fallet, Mathieu;Gorvel, Jean-Pierre
背景与目的：小肠的Peyer’s patches （PPs）是抗原取样和诱导部位，有助于建立粘膜免疫。腔内抗原通过滤泡相关上皮的特化上皮M细胞从PPs的粘膜表面转运到上皮下穹窿（SED）。在SED的树突状细胞（dc）中，有一些表达高水平的溶菌酶（LysoDC），具有很强的吞噬活性，它们处于吸收这些抗原的理想位置。我们研究了溶糖蛋白在体内捕获腔内抗原的机制。方法：将增强的绿色荧光蛋白基因插入到溶菌酶M位点（lys-EGFP小鼠）的小鼠PPs外植体上，采用双光子显微镜对其进行荧光检测。结果：LysoDC通过m细胞特异性的跨细胞孔将树突延伸到肠腔。m细胞黏附分子、连接黏附分子- a和上皮细胞黏附分子被招募到跨细胞迁移位点。跨细胞树突扫描m细胞顶端表面和肠腔内容；它们能够在腔内取出致病菌和惰性颗粒，然后再缩回SED。结论：我们描述了发生在PPs中的抗原取样机制，涉及滤泡相关上皮的M细胞和上皮下穹窿的dc细胞之间的合作。这一过程可能会发展为针对粘膜的疫苗。
BACKGROUND & AIMS: Peyer's patches (PPs) of the small intestine are antigen sampling and inductive sites that help establish mucosal immunity. Luminal antigens are transported from the mucosal surface of PPs to the subepithelial dome (SED), through the specialized epithelial M cells of the follicle-associated epithelium. Among the SED resident dendritic cells (DCs), which are situated ideally for taking up these antigens, some express high levels of lysozyme (LysoDC) and have strong phagocytic activity. We investigated the mechanisms by which LysoDCs capture luminal antigens in vivo. METHODS: We performed 2-photon microscopy on explants of PPs from mice in which the enhanced green fluorescent protein gene was inserted into the lysozyme M locus (lys-EGFP mice), allowing fluorescence detection of LysoDC. RESULTS: LysoDC extended dendrites through M-cell-specific transcellular pores to the gut lumen. The M-cell adhesion molecules junctional adhesion molecule-A and epithelial cell adhesion molecule were recruited to sites of transcellular migration. Transcellular dendrites scanned the M-cell apical surface and the gut luminal content; they were able to take pathogenic bacteria and inert particles in the lumen before retracting back to the SED. CONCLUSIONS: We describe an antigen sampling mechanism that occurs in PPs and involves cooperation between M cells of the follicle-associated epithelium and DCs of the subepithelial dome. This process might be developed to target vaccines to the mucosa.