Ionocytes and CFTR Chloride Channel Expression in Normal and Cystic Fibrosis Nasal and Bronchial Epithelial Cells.

Paolo Scudieri,Luis J V Galietta,Francesca Santamaria,Fabiana Ciciriello,Federico Cresta,Arianna Venturini,Michele Genovese,Vincenzina Lucidi,Alessandro Palleschi,Marco Poeta,Emanuela Caci,Daniela Guidone,Ilaria Musante

doi:10.3390/cells9092090

Abstract

The airway epithelium contains ionocytes, a rare cell type with high expression of Forkhead Box I1 (FOXI1) transcription factor and Cystic Fibrosis Transmembrane conductance Regulator (CFTR), a chloride channel that is defective in cystic fibrosis (CF). Our aim was to verify if ionocyte development is altered in CF and to investigate the relationship between ionocytes and CFTR-dependent chloride secretion. We collected nasal cells by brushing to determine ionocyte abundance. Nasal and bronchial cells were also expanded in vitro and reprogrammed to differentiated epithelia for morphological and functional studies. We found a relatively high (~3%) ionocyte abundance in ex vivo nasal samples, with no difference between CF and control individuals. In bronchi, ionocytes instead appeared very rarely as previously reported, thus suggesting a possible proximal–distal gradient in human airways. The difference between nasal and bronchial epithelial cells was maintained in culture, which suggests an epigenetic control of ionocyte development. In the differentiation phase of the culture procedure, we used two media that resulted in a different pattern of CFTR expression: confined to ionocytes or more broadly expressed. CFTR function was similar in both conditions, thus indicating that chloride secretion equally occurs irrespective of CFTR expression pattern.

Highlights

The surface of the airways is covered by an epithelial layer composed of a variety of different cell types [1]
Each dot represents the mean percentage of ionocytes over total cells in a single individual (n = 18 and 22 for non-cystic fibrosis (CF) and CF samples, respectively). (D) Representative images from a nasal sample devoid of ionocytes and with CFTR expressed in ciliated cells
Ionocytes were found in the human airway epithelium as a rare cell type characterized by high expression of CFTR, the Cl− channel that is defective in CF [23,24]

Summary

Introduction

The surface of the airways is covered by an epithelial layer composed of a variety of different cell types [1]. Ciliated cells constitute the most abundant cells in proximal airways. Goblet cells, devoted to the secretion of mucins, are relatively rare, but their number increases as a response to inflammation. There are club (secretory) cells, much more frequent in the epithelium of distal airways, that secrete mucins and other macromolecules with a protective function [5,6]. Continuous regeneration of ciliated, goblet, and secretory cells is provided by basal stem cells in the large airways [7,8,9,10]. Club cells may have themselves the ability to differentiate into other cell types [11]

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Conclusion