Human Neonatal Fc Receptor Mediates Transport of IgG into Luminal Secretions for Delivery of Antigens to Mucosal Dendritic Cells

Yoshida, Masaru; Claypool, Steven M.; Wagner, Jessica; Mizoguchi, Emiko; Mizoguchi, Atsushi; Roopenian, Derry C.; Lencer, Wayne I.; Blumberg, Richard S.

doi:10.1016/j.immuni.2004.05.007

Cited by 411 publications

(390 citation statements)

References 45 publications

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“…In species with abundant maternal IgG in breast milk, uptake of IgG-Ag immune complexes by epithelial cells can similarly achieve the transport of Ags to mucosal tolerogenic DC for appropriate hyporesponsive shaping. This is consistent with a study that showed that the IgG-specific Fc receptor (neonatal Fc receptor, FcRn) is expressed by epithelial cells in the intestine and airways, and can mediate IgG transport in both directions across epithelial barriers (84).…”

Section: Siga and Intestinal Homeostasissupporting

confidence: 92%

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

Corthésy¹

2007

The Journal of Immunology

193

148

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An important activity of mucosal surfaces is the production of Ab referred to as secretory IgA (SIgA). SIgA serves as the first line of defense against microorganisms through a mechanism called immune exclusion. In addition, SIgA adheres selectively to M cells in intestinal Peyer’s patches, thus mediating the transepithelial transport of the Ab molecule from the intestinal lumen to underlying gut-associated organized lymphoid tissue. In Peyer’s patches, SIgA binds and is internalized by dendritic cells in the subepithelial dome region. When used as carrier for Ags in oral immunization, SIgA induces mucosal and systemic responses associated with production of anti-inflammatory cytokines and limits activation of dendritic cells. In terms of humoral immunity at mucosal surfaces, SIgA appears thus to combine properties of a neutralizing agent (immune exclusion) and of a mucosal immunopotentiator inducing effector immune responses in a noninflammatory context favorable to preserve local homeostasis of the gastrointestinal tract.

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Section: Siga and Intestinal Homeostasissupporting

confidence: 92%

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

Corthésy¹

2007

The Journal of Immunology

193

148

View full text Add to dashboard Cite

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“…However, the 10 role of breast milk IgG in the defense against other pathogens has not been studied. Mouse 11 experiments indicate that breast milk IgG can cross the gut barrier through FcRn and can 12 thereby promote the transport of IgG-antigen immune complexes and stimulate immune 13 response to antigens and pathogens (60,(111)(112)(113)(114). Whether this process occurs in humans is 14…”

Section: Breast Milk Igg 23mentioning

confidence: 99%

Maternal immunisation: collaborating with mother nature

Marchant

Sadarangani

Garand

et al. 2017

The Lancet Infectious Diseases

156

124

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Maternal immunization offers much hope to substantially reduce morbidity and mortality from infectious diseases after birth. The success of tetanus, influenza and pertussis immunization during pregnancy has led to consideration of additional maternal immunization strategies to prevent Group B Streptococcus (GBS) and respiratory syncytial virus (RSV) infections, among others. However, there remain multiple gaps in our knowledge regarding the immunobiology of maternal immunization that prevent optimal design and application of this successful public health intervention. An innovative landscape analysis was therefore undertaken to identify research priorities. Key topics were delineated through review of the published literature, consultation with vaccine developers and regulatory agencies, and a collaborative workshop gathering experts across several current maternal immunization initiatives -GBS, RSV, pertussis, and influenza. Finally, a global online survey prioritized the identified knowledge gaps based on expert opinion regarding their importance and relevance. This article presents the results of this worldwide landscape analysis and discusses the identified research gaps.

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“…FcRn has been detected in numerous types of polarized epithelia, including those from the intestines, lung, breast, and kidney, as well as other parenchymal cells, including hepatocytes, endothelial cells, and hematopoietic cells, where it is expressed in dendritic cells, monocytes, macrophages, polymorphonuclear leukocytes, and, perhaps, B cells (7,8). FcRn protects monomeric IgG and albumin from degradation in both parenchymal and hematopoietic cells, is responsible for the bidirectional transcytosis of IgG and IgG antigen/antibody complexes across polarized epithelia, and, finally, directs immune complexes to lysosomes in dendritic cells for facilitation of antigen presentation (9,10).…”

mentioning

confidence: 99%

N-Glycan Moieties in Neonatal Fc Receptor Determine Steady-state Membrane Distribution and Directional Transport of IgG

Kuo

Muinck

Claypool

et al. 2009

Journal of Biological Chemistry

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The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I-related molecule known to protect IgG and albumin from catabolism and transport IgG across polarized epithelial cells in a bidirectional manner. Previous studies have shown species-specific differences in ligand binding, IgG transport direction, and steady-state membrane distribution when expressed in polarized epithelial cells. We hypothesized that these differences may be due to the additional N-glycans expressed on the rat Mutant human FcRn clones that contained additional N-glycan side-chain modifications, including that which was fully rodentized, still exhibited specificity for human IgG and failed to bind to mouse IgG. At steady state, the mutant human FcRn with additional N-glycans redistributed to the apical cell surface similar to that of rat FcRn. Furthermore, the rodentized human FcRn exhibited a reversal of IgG transport with predominant transcytosis from an apical-to-basolateral direction, which resembled that of the rat FcRn isoform. These studies show that the N-glycans in FcRn contribute significantly to the steady-state membrane distribution and direction of IgG transport in polarized epithelia. The neonatal Fc receptor (FcRn)2 was originally proposed by Brambell and colleagues to be the Fc receptor responsible for transfer of IgG through neonatal rodent intestinal epithelium and yolk sac of pregnant rabbits more than three decades ago (1). These functional properties were confirmed to be mediated by FcRn with the subsequent isolation from neonatal rat intestinal brush borders followed by the cloning of the rat homologue identified as a 50-kDa major histocompatibility complex class I-related heavy chain in non-covalent association with a 12-kDa subunit consistent with

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Human Neonatal Fc Receptor Mediates Transport of IgG into Luminal Secretions for Delivery of Antigens to Mucosal Dendritic Cells

Cited by 411 publications

References 45 publications

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

Maternal immunisation: collaborating with mother nature

N-Glycan Moieties in Neonatal Fc Receptor Determine Steady-state Membrane Distribution and Directional Transport of IgG

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