Department of Molecular Biology and Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea.
Eur J Immunol. 2011 Nov;41(11):3219-29. doi: 10.1002/eji.201141592. Epub 2011 Oct 18.
In the mucosal immune system, M cells are known as specialized epithelial cells that take up luminal antigens, although the receptors on M cells and the mechanism of antigen uptake into M cells are not well-understood. Here, we report the expression of the complement C5a receptor (C5aR) on the apical surface of M cells. C5ar mRNA expression in co-cultured Caco-2 human M-like cells was six-fold higher than in mono-cultured cells. C5aR expression was detected together with glycoprotein 2, an M-cell-specific protein, on the apical surface of M-like cells and mouse Peyer's patch M cells. Interestingly, after oral administration of Yersinia enterocolitica which expresses outer membrane protein H (OmpH) that is homologous to the Skp α1 domain of Escherichia coli, a ligand of C5aR, dense clustering and phosphorylation of C5aR were detected in M cells. Finally, targeted antigen delivery to M cells using C5aR as a receptor was achieved using the OmpH α1 of Y. enterocolitica such that the induction of ligand-conjugated antigen-specific immune responses was confirmed in mice after oral immunization of the OmpH β1α1-conjugated antigen. Collectively, we identified C5aR expression on M cells and suggest that C5aR could be used as a target receptor for mucosal antigen delivery.
在黏膜免疫系统中，M 细胞被认为是专门摄取腔抗原的上皮细胞，尽管 M 细胞上的受体和抗原摄取到 M 细胞的机制尚未完全了解。在这里，我们报告了补体 C5a 受体 (C5aR) 在 M 细胞顶表面的表达。与单核培养细胞相比，共培养的 Caco-2 人 M 样细胞中 C5ar mRNA 的表达高 6 倍。C5aR 表达与 M 样细胞和小鼠派尔集合淋巴结 M 细胞顶表面的糖蛋白 2（一种 M 细胞特异性蛋白）一起检测到。有趣的是，在口服表达与大肠杆菌 Skpα1 结构域同源的外膜蛋白 H (OmpH) 的肠侵袭性大肠杆菌后，C5aR 在 M 细胞中检测到密集聚集和磷酸化。最后，使用 C5aR 作为受体，通过使用肠侵袭性大肠杆菌的 OmpHα1 实现了针对 M 细胞的靶向抗原递送至 M 细胞，在口服免疫 OmpHβ1α1 缀合抗原后，在小鼠中证实了配体缀合的抗原特异性免疫反应的诱导。总之，我们鉴定了 M 细胞上的 C5aR 表达，并提出 C5aR 可作为黏膜抗原递送至的靶受体。
