Journal article
Il-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption
The Journal of clinical investigation, Vol.134(21), e181995
11/01/2024
DOI: 10.1172/JCI181995
PMCID: PMC11527443
PMID: 39255033
Abstract
The airway surface liquid (ASL) plays a crucial role in lung defense mechanisms, and its composition and volume are regulated by the airway epithelium. The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in a rare airway epithelial cell type called an ionocyte. Recently, we demonstrated that ionocytes can increase liquid absorption through apical CFTR and basolateral barttin/chloride channels, while airway secretory cells mediate liquid secretion through apical CFTR channels and basolateral NKCC1 transporters. Th2-driven (IL-4/IL-13) airway diseases, such as asthma, cause goblet cell metaplasia, accompanied by increased mucus production and airway secretions. In this study, we investigate the effect of IL-13 on chloride and liquid transport performed by ionocytes. IL-13 treatment of human airway epithelia was associated with reduced epithelial liquid absorption rates and increased ASL volume. Additionally, IL-13 treatment reduced the abundance of CFTR-positive ionocytes and increased the abundance of CFTR-positive secretory cells. Increasing ionocyte abundance attenuated liquid secretion caused by IL-13. Finally, CFTR-positive ionocytes were less common in asthma and COPD and associated with airflow obstruction. Our findings suggest that loss of CFTR in ionocytes contributes to the liquid secretion observed in IL-13-mediated airway diseases.
Details
- Title: Subtitle
- Il-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption
- Creators
- Guillermo S. Romano IbarraLei Lei - University of IowaWenjie Yu - University of Iowa, Internal MedicineAndrew L. Thurman - University of IowaNicholas D. GansemerDavid K. Meyerholz - University of IowaAlejandro A. Pezzulo - University of IowaPaul B. McCray - University of IowaIan M. Thornell - University of IowaDavid A. Stoltz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.134(21), e181995
- DOI
- 10.1172/JCI181995
- PMID
- 39255033
- PMCID
- PMC11527443
- NLM abbreviation
- J Clin Invest
- ISSN
- 1558-8238
- eISSN
- 1558-8238
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Grant note
- NIH: HL091842, GM007337, GM139776, HL007638, HL152960 Gilead Sciences Research Scholars Program in Cystic Fibrosis AwardUniversity of Iowa Health Care Distinguished Scholars ProgramCystic Fibrosis Foundation (Iowa CFF Research Development Program)
We thank M. Welsh and J. Zabner for excellent feedback and D. Voigt for assistance with scRNA-Seq analysis. This work was supported, in part, by the NIH (HL091842, GM007337, GM139776, HL007638, and HL152960) , a Gilead Sciences Research Scholars Program in Cystic Fibrosis Award (to IMT) , the University of Iowa Health Care Distinguished Scholars Program (to DAS) , and the Cystic Fibrosis Foundation (Iowa CFF Research Development Program) .
- Language
- English
- Electronic publication date
- 09/10/2024
- Date published
- 11/01/2024
- Academic Unit
- Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Critical Care; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984702847602771
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