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Special Issue "The Role of Airway Epithelial Cells in Health and Disease"

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Special Issue Editors

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Guest Editor

Biosciences Institute, University Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
Interests: epithelial ion transport; ion channels and transporters; cell signaling; pH regulation; cystic fibrosis; pancreatitis
Special Issues, Collections and Topics in MDPI journals

Dr. Carlos A. Flores

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Guest Editor

Centro de Estudios Científicos and Universidad San Sebastián, Valdivia, Chile
Interests: epithelial ion transport; ion channels and transporters; muco-obstructive diseases; airways; intestine

Special Issue Information

Dear Colleagues,

It is well established that the airway epithelium provides more than just a physical barrier that protects the body from inhaled pathogens. Airway epithelial cells are crucial for actively maintaining airway surface liquid homeostasis, mucociliary transport, antigen processing, and pathogen sensing, to give just a few examples. A better understanding of the myriad roles played by airway epithelial cells has been accelerated in recent years by the identification of distinct epithelial cell populations that constitute, and are resident in, the human airways, primarily driven by advances in single-cell RNA sequencing. This information has also been crucial in defining epithelial cell lineage and differentiation, as well as identifying rarer epithelial cells such as the ionocyte. Despite all that we have learned, many questions remain. For example, what is the functional role of rarer epithelial cells (ionocyte, brush and PNEC) in airways physiology, and do they interact with more abundant epithelial cells, such as secretory and multiciliated cells, alveolar and/or non-epithelial cells? If they do, how do they interact, and what are the implications for normal airway function and disease pathogenesis? Which epithelial cells should we target for the treatment of common airway diseases, and what about during tissue repair after infection? What is the importance of the differences in epithelial cellular heterogeneity and gene expression along the proximal to distal airways, and what are the consequences for airway disease and its treatment?

The purpose of this Special issue is to highlight the important role played by distinct types of airway epithelial cells, and how this information is being harnessed to develop new therapeutic strategies for important diseases such as cystic fibrosis, COVID-19, asthma and pulmonary fibrosis. The goal of this Issue is to provide a broad scope that includes research papers and reviews related to the functional roles of epithelial cells in airway health and disease.

Dr. Michael Gray
Dr. Carlos A. Flores
Guest Editors

Manuscript Submission Information

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Keywords

airway epithelial cell types
airway homeostasis
airway defense
mucociliary transport
ionocytes
brush cells
basal cells
alveolar cells
chronic lung disease
epithelial repair

Published Papers (2 papers)

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Research

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Open AccessArticle

The Impact of CC16 on Pulmonary Epithelial-Driven Host Responses during Mycoplasma pneumoniae Infection in Mouse Tracheal Epithelial Cells

and

Cells 2023, 12(15), 1984; https://doi.org/10.3390/cells12151984 - 01 Aug 2023

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Abstract

Club Cell Secretory Protein (CC16) plays many protective roles within the lung; however, the complete biological functions, especially regarding the pulmonary epithelium during infection, remain undefined. We have previously shown that CC16-deficient (CC16^−/−) mouse tracheal epithelial cells (MTECs) have enhanced Mp burden compared to CC16-sufficient (WT) MTECs; therefore, in this study, we wanted to further define how the pulmonary epithelium responds to infection in the context of CC16 deficiency. Using mass spectrometry and quantitative proteomics to analyze proteins secreted apically from MTECs grown at an air–liquid interface, we investigated the protective effects that CC16 elicits within the pulmonary epithelium during Mycoplasma pneumoniae (Mp) infection. When challenged with Mp, WT MTECs have an overall reduction in apical protein secretion, whereas CC16^−/− MTECs have increased apical protein secretion compared to their unchallenged controls. Following Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessment, many of the proteins upregulated from CC16^−/− MTECS (unchallenged and during Mp infection) were related to airway remodeling, which were not observed by WT MTECs. These findings suggest that CC16 may be important in providing protection within the pulmonary epithelium during respiratory infection with Mp, which is the major causative agent of community-acquired pneumoniae. Full article

(This article belongs to the Special Issue The Role of Airway Epithelial Cells in Health and Disease)

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Graphical abstract

Review

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Open AccessReview

Inflammation as a Regulator of the Airway Surface Liquid pH in Cystic Fibrosis

Tayyab Rehman

and

Michael J. Welsh

Cells 2023, 12(8), 1104; https://doi.org/10.3390/cells12081104 - 07 Apr 2023

Viewed by 1401

Abstract

The airway surface liquid (ASL) is a thin sheet of fluid that covers the luminal aspect of the airway epithelium. The ASL is a site of several first-line host defenses, and its composition is a key factor that determines respiratory fitness. Specifically, the acid–base balance of ASL has a major influence on the vital respiratory defense processes of mucociliary clearance and antimicrobial peptide activity against inhaled pathogens. In the inherited disorder cystic fibrosis (CF), loss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channel function reduces HCO₃⁻ secretion, lowers the pH of ASL (pH_ASL), and impairs host defenses. These abnormalities initiate a pathologic process whose hallmarks are chronic infection, inflammation, mucus obstruction, and bronchiectasis. Inflammation is particularly relevant as it develops early in CF and persists despite highly effective CFTR modulator therapy. Recent studies show that inflammation may alter HCO₃⁻ and H⁺ secretion across the airway epithelia and thus regulate pH_ASL. Moreover, inflammation may enhance the restoration of CFTR channel function in CF epithelia exposed to clinically approved modulators. This review focuses on the complex relationships between acid–base secretion, airway inflammation, pH_ASL regulation, and therapeutic responses to CFTR modulators. These factors have important implications for defining optimal ways of tackling CF airway inflammation in the post-modulator era. Full article

(This article belongs to the Special Issue The Role of Airway Epithelial Cells in Health and Disease)

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