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.
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http://dx.doi.org/10.1172/JCI6968 | DOI Listing |
Mucosal Immunol
January 2025
Weill Cornell Medicine Department of Pediatrics, Division of Infectious Disease, New York, NY, USA. Electronic address:
Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates.
View Article and Find Full Text PDFSci Transl Med
January 2025
First Department of Medicine, Cardiology, TUM University Hospital, Technical University of Munich, School of Medicine and Health, Munich 81675, Germany.
In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.
View Article and Find Full Text PDFCardiovasc Diabetol
January 2025
Univ. Bordeaux, Inserm, Biology of Cardiovascular Diseases, U1034, CHU de Bordeaux, 1, Avenue de Magellan, Entrée par l'Hôpital Haut-Lévêque, 33604, Pessac, France.
Background: Chronic Limb-Threatening Ischemia (CLTI) represents the most advanced stage of Peripheral Artery Disease (PAD) and is associated with dire prognosis, characterized by a substantial risk of limb amputation and diminished life expectancy. Despite significant advancements in therapeutic interventions, the underlying mechanisms precipitating the progression of PAD to CLTI remain elusive.
Methods: Considering diabetes is one of the main risk factors contributing to PAD exacerbation into CLTI, we compared hind limb ischemia recovery in HFD STZ vs.
J Nanobiotechnology
January 2025
School of First Clinical Medical, Ningxia Medical University, Yinchuan, 750004, China.
Background: Helicobacter pylori (H. pylori), a specific bacterium capable of surviving in the acidic environment of the stomach, has been recognized as a group of causative agents of gastric cancer. Therefore, the development of mucosal vaccines against H.
View Article and Find Full Text PDFBiomaterials
January 2025
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, Houston Methodist Hospital, Houston, TX, USA; Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. Electronic address:
Contrasting findings are presented in the literature regarding the influence of foreign body response (FBR) on drug release from implantable drug delivery systems. To this end, here we sought direct evidence of the effect of the fibrotic tissue on subcutaneous drug release from long-acting drug delivery implants. Specifically, we investigated the pharmacokinetic impact of fibrotic encapsulation on a small molecule drug, islatravir (293 Da), and a large protein, IgG (150 kDa), administered via biocompatible implants.
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