FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?
by
Emilie Bequignon 1,2,3,4,*, Christine Dhommée 5, Christelle Angely 2,3,4, Lucie Thomas 6, Mathieu Bottier 2,3,4, Estelle Escudier 6,7,8, Daniel Isabey 2,3,4, André Coste 1,2,3,4, Bruno Louis 2,3,4, Jean-François Papon 2,4,9,10,† and Valérie Gouilleux-Gruart 5,11,†
Emilie Bequignon 1,2,3,4,*, Christine Dhommée 5, Christelle Angely 2,3,4, Lucie Thomas 6, Mathieu Bottier 2,3,4, Estelle Escudier 6,7,8, Daniel Isabey 2,3,4, André Coste 1,2,3,4, Bruno Louis 2,3,4, Jean-François Papon 2,4,9,10,† and Valérie Gouilleux-Gruart 5,11,†
1
AP-HP, Hôpital Henri Mondor et Centre Hospitalier Intercommunal de Créteil, service d’Oto-Rhino-Laryngologie et de Chirurgie cervico-faciale, 94010 Créteil, France
2
INSERM, U955, 94010 Créteil, France
3
Université Paris-Est, Faculté de Médecine, F-94010 Créteil, France
4
CNRS, ERL 7240, 94010 Créteil, France
5
Université de Tours, EA 7501 GICC, F-37032 Tours, France
6
Inserm U933, 75012 Paris, France
7
Université Pierre et Marie Curie, Faculté de Médecine, 75005 Paris, France
8
AP-HP Hôpital Armand-Trousseau, Service de génétique et d’embryologie médicale, 75012 Paris, France
9
AP-HP, Hôpital Bicêtre, Service d’Oto-Rhino-Laryngologie et de Chirurgie cervico-faciale, 94270 Le Kremlin-Bicêtre, France
10
Faculté de Médecine, Université Paris-Sud, F-94275 Le Kremlin-Bicêtre, France
11
CHRU de TOURS, Laboratoire d’Immunologie, F-37032 Tours, France
*
Author to whom correspondence should be addressed.
†
These authors have contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(6), 1379; https://doi.org/10.3390/ijms20061379
Received: 18 January 2019 / Revised: 11 March 2019 / Accepted: 12 March 2019 / Published: 19 March 2019
(This article belongs to the Section Molecular Immunology)
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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Keywords:
neonatal Fc receptor; chronic rhinosinusitis with nasal polyps; transcytosis; human nasal epithelial cells; monoclonal antibodies
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MDPI and ACS Style
Bequignon, E.; Dhommée, C.; Angely, C.; Thomas, L.; Bottier, M.; Escudier, E.; Isabey, D.; Coste, A.; Louis, B.; Papon, J.-F.; Gouilleux-Gruart, V. FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy? Int. J. Mol. Sci. 2019, 20, 1379.
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