Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria
Masaru Yoshida, … , Wayne I. Lencer, Richard S. Blumberg
Masaru Yoshida, … , Wayne I. Lencer, Richard S. Blumberg
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2142-2151. https://doi.org/10.1172/JCI27821.
View: Text | PDF
Research Article Gastroenterology

Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria

Abstract

The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. Selective expression of FcRn in the epithelium is shown here to be associated with secretion of IgG into the lumen that allows for defense against an epithelium-associated pathogen (Citrobacter rodentium). This pathway of host resistance to a bacterial pathogen as mediated by FcRn involves retrieval of bacterial antigens from the lumen and initiation of adaptive immune responses in regional lymphoid structures. Epithelial-associated FcRn, through its ability to secrete and absorb IgG, may thus integrate luminal antigen encounters with systemic immune compartments and as such provide essential host defense and immunoregulatory functions at the mucosal surfaces.

Authors

Masaru Yoshida, Kanna Kobayashi, Timothy T. Kuo, Lynn Bry, Jonathan N. Glickman, Steven M. Claypool, Arthur Kaser, Takashi Nagaishi, Darren E. Higgins, Emiko Mizoguchi, Yoshio Wakatsuki, Derry C. Roopenian, Atsushi Mizoguchi, Wayne I. Lencer, Richard S. Blumberg

×

Figure 1

Absence of intestinal luminal IgG in FcRn–/– mice.

Options: View larger image (or click on image) Download as PowerPoint
Absence of intestinal luminal IgG in FcRn–/– ...
(A) The construct for the Tg IFABP-mFcRnTg/mβ2mTg mouse, designed to express mFcRn and mβ2m under the control of the IFABP. (B) Increased mFcRn expression in epithelial cells of IFABP-mFcRnTg/mβ2mTg (Tg) mouse. RNA was extracted from epithelial cells of upper and lower small intestines (USI and LSI, respectively) and cecum in 6-week-old IFABP-mFcRnTg/mβ2mTg founder BALB/c mice and littermate WT BALB/c mice and subjected to RT-PCR. (C and D) Immunohistochemical analysis of lower small intestine in WT (C) and IFABP-mFcRnTg/mβ2mTg mice (D). Arrows indicate staining of FcRn. (E–H) The levels of Igs secreted into the intestinal lumen. Secretory IgM (E), dimeric IgA (F), IgG1 (G), and IgG2a (H) were measured by ELISA. The mean ± SD are shown for each group (n = 8). *P < 0.05. (I) The levels of Igs (IgG1, IgG2a, IgG2b, IgG3, IgA, IgM, and IgE) secreted into the lumen of the indicated mouse strains on a C57BL/6 background were measured by a cytometric bead array.