Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell Line

被引:326
作者
Dickinson, BL
Badizadegan, K
Wu, Z
Ahouse, JC
Zhu, XP
Simister, NE
Blumberg, RS
Lencer, WI
机构
[1] Harvard Med Sch, Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Dept Pediat, Boston, MA 02115 USA
[2] Harvard Med Sch, Childrens Hosp, Dept Pathol, Boston, MA 02115 USA
[3] Brandeis Univ, Rosenstiel Ctr Basic Biomed Sci, WM Kech Inst Cellular Visualizat, Waltham, MA 02254 USA
[4] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA
[5] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA
[6] Harvard Med Sch, Dept Med, Boston, MA 02115 USA
[7] Harvard Digest Dis Ctr, Boston, MA 02115 USA
关键词
D O I
10.1172/JCI6968
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:903 / 911
页数:9
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