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.
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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

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Figure 4

Induction of immune response toC. rodentium –derived antigen in the presence of circulating IgG and FcRn in intestinal epithelial cells.

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Induction of immune response toC. rodentium ...
(A and B) The effect of FcRn-mediated IgG transport into the intestinal lumen in C. rodentium infection. Body weight changes (A) and CFU of C. rodentium in feces 21 days after infection (B) in IFABP-mFcRnTg/mβ2mTg/FcRn–/– and FcRn–/– C57BL/6 mice with i.v. injection of anti–C. rodentium IgG or control IgG. Mean ± SD are shown for each group (n = 6). (C) Establishment of a genetically engineered C. rodentium strain that constitutively produces an OVA fragment. The immunoblot confirms the expression of the OVA fragment by C. rodentium. (D) Summary of the experimental protocol, with the inoculation of C. rodentium–OVA or control bacteria, the injection of anti–C. rodentium IgG or control IgG, and the adoptive transfer of CD45.1+CD4+OVA-specific T cells from CD45.1+OT-II mice. (E) The number of OVA-specific CD4+ T cells in the MLNs in IFABP-mFcRnTg/mβ2mTg/FcRn–/– and FcRn–/– mice increased in the presence of anti–C. rodentium IgG or control IgG (n = 3). Arrows indicate increasing rounds of cell division. (F and G) Cytokine production in OVA-specific CD4+ T cells purified from the MLNs and cultured with OVA for 48 hours in vitro. Cytokine production of IFN-γ (F) and IL-4 (G) was measured by ELISA. Mean ± SD are shown for each group (n = 4). *P < 0.05.