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FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?

Monoclonal antibodies (mAbs) are promising therapies to treat airway chronic inflammatory disease (asthma or nasal polyps). To date, no study has specifically assessed, in vitro, the potential function of neonatal Fc receptor (FcRn) in IgG transcytosis through the human nasal airway epithelium. The...

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Autores principales: Bequignon, Emilie, Dhommée, Christine, Angely, Christelle, Thomas, Lucie, Bottier, Mathieu, Escudier, Estelle, Isabey, Daniel, Coste, André, Louis, Bruno, Papon, Jean-François, Gouilleux-Gruart, Valérie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470570/
https://www.ncbi.nlm.nih.gov/pubmed/30893823
http://dx.doi.org/10.3390/ijms20061379
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author Bequignon, Emilie
Dhommée, Christine
Angely, Christelle
Thomas, Lucie
Bottier, Mathieu
Escudier, Estelle
Isabey, Daniel
Coste, André
Louis, Bruno
Papon, Jean-François
Gouilleux-Gruart, Valérie
author_facet Bequignon, Emilie
Dhommée, Christine
Angely, Christelle
Thomas, Lucie
Bottier, Mathieu
Escudier, Estelle
Isabey, Daniel
Coste, André
Louis, Bruno
Papon, Jean-François
Gouilleux-Gruart, Valérie
author_sort Bequignon, Emilie
collection PubMed
description Monoclonal antibodies (mAbs) are promising therapies to treat airway chronic inflammatory disease (asthma or nasal polyps). To date, no study has specifically assessed, in vitro, the potential function of neonatal Fc receptor (FcRn) in IgG transcytosis through the human nasal airway epithelium. The objective of this study was to report the in vitro expression and function of FcRn in nasal human epithelium. FcRn expression was studied in an air–liquid interface (ALI) primary culture model of human nasal epithelial cells (HNEC) from polyps. FcRn expression was characterized by quantitative RT-PCR, western blot, and immunolabeling. The ability of HNECs to support mAb transcytosis via FcRn was assessed by transcytosis assay. This study demonstrates the expression of FcRn mRNA and protein in HNEC. We report a high expression of FcRn in the cytosol of ciliated, mucus, and basal cells by immunohistochemistry with a higher level of FcRn proteins in differentiated HNEC. We also proved in vitro transepithelial delivery of an IgG1 therapeutic mAb with a dose–response curve. This is the first time that FcRn expression and mAb transcytosis has been shown in a model of human nasal respiratory epithelium in vitro. This study is a prerequisite for FcRn-dependent nasal administration of mAbs.
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spelling pubmed-64705702019-04-26 FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy? Bequignon, Emilie Dhommée, Christine Angely, Christelle Thomas, Lucie Bottier, Mathieu Escudier, Estelle Isabey, Daniel Coste, André Louis, Bruno Papon, Jean-François Gouilleux-Gruart, Valérie Int J Mol Sci Article Monoclonal antibodies (mAbs) are promising therapies to treat airway chronic inflammatory disease (asthma or nasal polyps). To date, no study has specifically assessed, in vitro, the potential function of neonatal Fc receptor (FcRn) in IgG transcytosis through the human nasal airway epithelium. The objective of this study was to report the in vitro expression and function of FcRn in nasal human epithelium. FcRn expression was studied in an air–liquid interface (ALI) primary culture model of human nasal epithelial cells (HNEC) from polyps. FcRn expression was characterized by quantitative RT-PCR, western blot, and immunolabeling. The ability of HNECs to support mAb transcytosis via FcRn was assessed by transcytosis assay. This study demonstrates the expression of FcRn mRNA and protein in HNEC. We report a high expression of FcRn in the cytosol of ciliated, mucus, and basal cells by immunohistochemistry with a higher level of FcRn proteins in differentiated HNEC. We also proved in vitro transepithelial delivery of an IgG1 therapeutic mAb with a dose–response curve. This is the first time that FcRn expression and mAb transcytosis has been shown in a model of human nasal respiratory epithelium in vitro. This study is a prerequisite for FcRn-dependent nasal administration of mAbs. MDPI 2019-03-19 /pmc/articles/PMC6470570/ /pubmed/30893823 http://dx.doi.org/10.3390/ijms20061379 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bequignon, Emilie
Dhommée, Christine
Angely, Christelle
Thomas, Lucie
Bottier, Mathieu
Escudier, Estelle
Isabey, Daniel
Coste, André
Louis, Bruno
Papon, Jean-François
Gouilleux-Gruart, Valérie
FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?
title FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?
title_full FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?
title_fullStr FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?
title_full_unstemmed FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?
title_short FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?
title_sort fcrn-dependent transcytosis of monoclonal antibody in human nasal epithelial cells in vitro: a prerequisite for a new delivery route for therapy?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470570/
https://www.ncbi.nlm.nih.gov/pubmed/30893823
http://dx.doi.org/10.3390/ijms20061379
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