ArticleThe Journal of clinical investigation2023
CFTR-rich ionocytes mediate chloride absorption across airway epithelia.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Understanding Nasal Polyposis: The Roles of Ion Channels, Inflammation, Ionocytes, and Prostaglandin E2-The IJournal of clinical medicine · 2026Article
- Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Base editing and nanoparticle transfection of airway cell types essential for treatment of cystic fibrosis.JCI insight · 2026Article
- Ascl3The Journal of physiology · 2026Article
- Exposing the Airway Surface to the Neonicotinoid Clothianidin Alters the Electrophysiological Properties of Human Airway Epithelia.ACS omega · 2026Article
- Specialized gas-exchange endothelium of the zebrafish gill.bioRxiv : the preprint server for biology · 2025Article
- Acquired cystic fibrosis transmembrane conductance regulator dysfunction.Pflugers Archiv : European journal of physiology · 2025Review
- Base editing and nanoparticle transfection of airway cell types essential for treatment of cystic fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Pulmonary Ionocytes at the Crossroads of Absorption and Secretion: Clues from the Ferret.American journal of respiratory and critical care medicine · 2025Article
- Ionocyte CFTR Coordinates Chloride Absorption and Secretion to Balance Airway Fluid.American journal of respiratory and critical care medicine · 2025Article
- Genetically engineered approaches to the treatment of cystic fibrosis.Biophysical reviews · 2025Review
- Isolation and Culture of Ferret Airway Stem Cells.Bio-protocol · 2025Article
- Novel Lung Cell-Penetrating Peptide Targets Alveolar Epithelial Type II Cells, Basal Cells, and Ionocytes.Pharmaceutics · 2025Article
- Effects of Elevated Glucose on Bacterial Respiratory Infections in Cystic Fibrosis and Chronic Airway Diseases.International journal of molecular sciences · 2025Review
- Article
- Single cell profiling of human airway identifies tuft-ionocyte progenitor cells displaying cytokine-dependent differentiation bias in vitro.Nature communications · 2025Article
- Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.Molecular and cellular pediatrics · 2025Review
- Innate Immunity and Asthma Exacerbations: Insights From Human Models.Immunological reviews · 2025Review
- CFTR as a therapeutic target for severe lung infection.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Do pulmonary ionocytes absorb chloride or secrete chloride?American journal of physiology. Cell physiology · 2025Review
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12 authors.
Funding
Abstract
The volume and composition of a thin layer of liquid covering the airway surface defend the lung from inhaled pathogens and debris. Airway epithelia secrete Cl- into the airway surface liquid through cystic fibrosis transmembrane conductance regulator (CFTR) channels, thereby increasing the volume of airway surface liquid. The discovery that pulmonary ionocytes contain high levels of CFTR led us to predict that ionocytes drive secretion. However, we found the opposite. Elevating ionocyte abundance increased liquid absorption, whereas reducing ionocyte abundance increased secretion. In contrast to other airway epithelial cells, ionocytes contained barttin/Cl- channels in their basolateral membrane. Disrupting barttin/Cl- channel function impaired liquid absorption, and overexpressing barttin/Cl- channels increased absorption. Together, apical CFTR and basolateral barttin/Cl- channels provide an electrically conductive pathway for Cl- flow through ionocytes, and the transepithelial voltage generated by apical Na+ channels drives absorption. These findings indicate that ionocytes mediate liquid absorption, and secretory cells mediate liquid secretion. Segregating these counteracting activities to distinct cell types enables epithelia to precisely control the airway surface. Moreover, the divergent role of CFTR in ionocytes and secretory cells suggests that cystic fibrosis disrupts both liquid secretion and absorption.
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