The gut cell wall is considered an impenetrable barrier to orally administrated polysaccharides. We recently reported a selective lymphatic route for Radix Astragali polysaccharide RAP to enter Peyer's patches (PPs) to trigger immune responses. However, how RAP enters PPs is unclear. Herein, we screened the intestinal epithelial cells of mice and found that the follicle-associated epithelium cells were specifically bound with FITC-RAP. Further studies in vitro and in vivo revealed that RAP was efficiently transported by microfold (M) cells. We also confirmed that M cell-transported RAP directly contacted dendritic cells. More importantly, for the first time, we verified this interesting M cell-mediated transcytosis of RAP in the human distal ileum. Mechanistically, we identified M cells to be the transporter cells that independently deliver RAP into the lymphatic system to trigger immune responses. This interesting transcytosis mechanism might apply to many other immunomodulatory polysaccharides orally dosed to human body.

肠细胞壁被认为是口服多糖的不可逾越的屏障。我们最近报道了黄芪多糖 RAP 进入派尔氏斑 (PPs) 以触发免疫反应的选择性淋巴途径。但是，RAP 是如何进入 PP 的还不清楚。在此，我们筛选了小鼠的肠上皮细胞，发现毛囊相关上皮细胞与 FITC-RAP 特异性结合。进一步的体外和体内研究揭示了RAP被微折叠（M）细胞有效运输。我们还证实 M 细胞转运的 RAP 直接接触树突状细胞。更重要的是，我们第一次验证了这种有趣的 M 细胞介导的 RAP 在人类回肠末端的转胞吞作用。从机制上讲，我们确定 M 细胞是独立地将 RAP 输送到淋巴系统以触发免疫反应的转运细胞。这种有趣的胞吞作用机制可能适用于许多其他口服给药于人体的免疫调节多糖。