Journal article
CFTR-rich ionocytes mediate chloride absorption across airway epithelia
The Journal of clinical investigation, Vol.133(20), e171268
10/2023
DOI: 10.1172/JCI171268
PMCID: PMC10575720
PMID: 37581935
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 CFTR (cystic fibrosis transmembrane conductance regulator) 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.
Details
- Title: Subtitle
- CFTR-rich ionocytes mediate chloride absorption across airway epithelia
- Creators
- Lei LeiSoumba TraoreGuillermo S Romano IbarraPhilip H KarpTayyab RehmanDavid K MeyerholzJoseph ZabnerDavid A StoltzPatrick L SinnMichael J WelshPaul B McCrayIan M Thornell
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.133(20), e171268
- DOI
- 10.1172/JCI171268
- PMID
- 37581935
- PMCID
- PMC10575720
- NLM abbreviation
- J Clin Invest
- ISSN
- 1558-8238
- eISSN
- 1558-8238
- Grant note
- name: NIH, award: DK054759, HL09184, HL133089, HL147366, HL152960; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation, award: Iowa CFF Research Development Program, SINN22G0, Harry Shwachman Clinical Investigator Award; DOI: 10.13039/100005564, name: Gilead Sciences, award: Gilead Sciences Research Scholars Program in Cystic Fibrosis Award; DOI: 10.13039/100000011, name: Howard Hughes Medical Institute, award: MJW investigator; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust, award: PBM supported by
- Language
- English
- Electronic publication date
- 08/15/2023
- Date published
- 10/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Critical Care; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984455656602771
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