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

Emilie Bequignon,Christine Dhommée,Bruno Louis,Mathieu Bottier,Valérie Gouilleux-Gruart,Jean-François Papon,Daniel Isabey,Lucie Thomas,Christelle Angely,Estelle Escudier,André Coste

doi:10.3390/ijms20061379

Abstract

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.

Highlights

FcRn, or neonatal receptor for the Fc portion of IgG, was first identified in 1964 by Brambell [1]
In the first part of this study, we evaluated the in vitro expression of FcRn in an air–liquid interface (ALI) model of primary culture of human nasal epithelial cells (HNEC) by quantitative RT-PCR, western blot, and immunolabeling
We report in vitro FcRn expression in HNEC in a differentiated model of ALI primary culture and demonstrate that FcRn expression is dependent on the degree of cell differentiation

Summary

Introduction

FcRn, or neonatal receptor for the Fc portion of IgG, was first identified in 1964 by Brambell [1]. The delivery of mAbs through the lower airways (aerosols were administered directly into the lungs through an endotracheal tube under general anesthesia) has been shown to be a promising development in the treatment of inflammatory respiratory diseases [20,21,22,23]. In line with these lung studies, Heidl et al demonstrated the ex vivo expression of FcRn in nasal mucosa of inferior turbinate (fixed tissue) [24], and Samson et al discussed FcRn-mediated transport through porcine nasal mucosa [25]. In the second part of the study, we evaluated the ability of HNEC to support mAb transcytosis

Objectives

Methods

Findings

Conclusion