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Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line
Bonny L. Dickinson, … , Richard S. Blumberg, Wayne I. Lencer
Bonny L. Dickinson, … , Richard S. Blumberg, Wayne I. Lencer
Published October 1, 1999
Citation Information: J Clin Invest. 1999;104(7):903-911. https://doi.org/10.1172/JCI6968.
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Article

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

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Abstract

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.

Authors

Bonny L. Dickinson, Kamran Badizadegan, Zhen Wu, Jeremy C. Ahouse, Xiaoping Zhu, Neil E. Simister, Richard S. Blumberg, Wayne I. Lencer

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Figure 1

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FcRn expression in normal adult human small intestine and human intestin...
FcRn expression in normal adult human small intestine and human intestinal epithelial cell lines. Western blots of total cellular protein (13 μg protein per lane, a; 10 μg protein per lane, b) isolated from the indicated source using affinity-purified rabbit antisera raised against amino acids 112–125 (a) or amino acids 174–188 (b). (c) RT-PCR detection of FcγRI transcripts. Total RNA (2 μg) from T84 (lanes 3 and 4), MOLT-4 (lanes 5 and 6; negative control), and U937 (lanes 1 and 2; positive control) cell lines was incubated with an oligo-dT primer with (odd-numbered lanes) or without (even-numbered lanes) avian myeloblastosis virus–RT (AMV-RT), and a nested PCR was performed with primers specific for FcγRI cDNA (top) or for β-actin (bottom).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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