Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells.
Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The mechanism by which IgG reaches luminal secretions and the function of IgG in these locations are unknown. Here, we find that the human neonatal Fc receptor (FcRn) is the vehicle that transports IgG across the intestinal epithelial barrier into the lumen where the IgG can bind cognate antigen. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. These results explain how IgG is secreted onto mucosal surfaces and scavenges luminal antigens for recognition by the immune system.
Yoshida
Masaru
M
Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Claypool
Steven M
SM
Wagner
Jessica S
JS
Mizoguchi
Emiko
E
Mizoguchi
Atsushi
A
Roopenian
Derry C
DC
Lencer
Wayne I
WI
Blumberg
Richard S
RS
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016764:Cell Polarity; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004285:Dogs; D004705:Endocytosis; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport; D011817:Rabbits; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000276:immunology
D000936:Antigen-Antibody Complex; D000941:Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D001613:beta 2-Microglobulin; D010047:Ovalbumin; C100688:Fc receptor, neonatal