Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell Line
Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell Line
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DOI：
10.1172/jci6968
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发表时间：
1999-10-01
影响因子：
15.9
通讯作者：
Lencer, WI
中科院分区：
文献类型：
--
作者：
Dickinson, BL;Badizadegan, K;Lencer, WI
MHC I 类相关 Fc 受体 FcRn 在新生啮齿类动物中介导母体 IgG 的肠道吸收，并通过受体介导的转胞吞作用介导人类母体 IgG 的经胎盘转运。在小鼠和大鼠中，肠上皮细胞中FcRn的表达仅限于哺乳期。然而，我们最近观察到 FcRn 在成人肠道中清晰表达，这表明 FcRn 在人类新生儿生命之外的肠道 IgG 运输中发挥着作用。我们使用极化的人肠道 T84 细胞系作为模型上皮来测试这一假设。免疫细胞化学数据显示，FcRn 以点状顶端模式存在于 T84 细胞中，类似于人小肠肠上皮细胞中的模式。溶质通量研究表明，FcRn 通过受体介导的转胞吞作用跨 T84 单层转运 IgG。运输是双向的，对 FcRn 具有特异性，并且依赖于内体酸化。这些数据定义了 IgG 跨上皮屏障转运的新型双向机制，该机制预测 FcRn 对粘膜表面免疫监视和宿主防御中 IgG 功能的重要影响。
The MHC class I-related Fc receptor, FcRn, mediates the intestinal absorption of maternal IgG in neonatal rodents and the transplacental transport of maternal IgG in humans by receptor-mediated transcytosis. In mice and rats, expression of FcRn in intestinal epithelial cells is limited to the suckling period. We have recently observed, however, clear expression of FcRn in the adult human intestine, suggesting a function for FcRn in intestinal IgG transport beyond neonatal life in humans. We tested this hypothesis using the polarized human intestinal T84 cell line as a model epithelium. Immunocytochemical data show that FcRn is present in T84 cells in a punctate apical pattern similar to that found in human small intestinal enterocytes. Solute flux studies show that FcRn transports IgG across T84 monolayers by receptor-mediated transcytosis. Transport is bidirectional, specific for FcRn, and dependent upon endosomal acidification. These data define a novel bidirectional mechanism of IgG transport across epithelial barriers that predicts an important effect of FcRn on IgG function in immune surveillance and host defense at mucosal surfaces.