AP-HP, Hôpital Henri Mondor et Centre Hospitalier Intercommunal de Créteil, service d'Oto-Rhino-Laryngologie et de Chirurgie cervico-faciale, 94010 Créteil, France.
INSERM, U955, 94010 Créteil, France.
Int J Mol Sci. 2019 Mar 19;20(6):1379. doi: 10.3390/ijms20061379.
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.
单克隆抗体（mAbs）是治疗气道慢性炎症性疾病（哮喘或鼻息肉）的有前途的疗法。迄今为止，尚无研究专门评估新生儿 Fc 受体（FcRn）在 IgG 经人鼻气道上皮细胞转运中的潜在功能。本研究的目的是报告 FcRn 在鼻人上皮细胞中的体外表达和功能。在鼻息肉的人鼻上皮细胞（HNEC）的气⁃液界面（ALI）原代培养模型中研究了 FcRn 的表达。通过定量 RT-PCR、western blot 和免疫标记法对 FcRn 的表达进行了特征分析。通过转胞吞作用测定评估了 HNEC 支持 mAb 经 FcRn 转胞吞的能力。本研究证明了 FcRn 在 HNEC 中的 mRNA 和蛋白表达。我们通过免疫组织化学报告了 FcRn 在纤毛、粘液和基底细胞的细胞质中的高表达，并且在分化的 HNEC 中 FcRn 蛋白水平更高。我们还证明了 IgG1 治疗性 mAb 的体外跨上皮传递具有剂量反应曲线。这是首次在体外人鼻呼吸上皮细胞模型中显示 FcRn 表达和 mAb 转胞吞作用。这项研究是 FcRn 依赖的鼻内给予 mAbs 的前提条件。
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