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Updated: May 7, 2026
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Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
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Highly Effective Modulator Therapies Restore Neutrophil Dysfunction in People with Cystic Fibrosis
Frank H Robledo-Avila1, Raul Rascon1, Alejandra Montanez-Barragan1
1Center for Microbe and Immunity Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.
Summary
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators like ETI restore neutrophil antimicrobial functions. This study shows CFTR modulators enhance neutrophil killing of microbes and NETs production in people with CF.
Area of Science:
- Immunology
- Cell Biology
- Medical Genetics
Background:
- Cystic fibrosis (CF) is a genetic disorder caused by a defective CF-transmembrane conductance regulator (CFTR) protein.
- People with CF (pwCF) experience chronic inflammation and are susceptible to opportunistic infections, partly due to impaired neutrophil function.
- CFTR modulators, such as the ETI combination (Elexacaftor, Tezacaftor, Ivacaftor), have improved clinical outcomes for pwCF, but their impact on neutrophil function is unclear.
Purpose of the Study:
- To investigate the role of CFTR in neutrophil function.
- To determine how CFTR modulators, specifically ETI, affect CF neutrophils.
- To elucidate the mechanisms by which ETI may restore antimicrobial functions in neutrophils from pwCF.
Main Methods:
- Demonstrated functional expression of CFTR in human neutrophils.
- Analyzed the effect of ETI on CFTR trafficking in CF neutrophils.
- Measured intracellular chloride levels, NADPH oxidase activity, and Neutrophil Extracellular Traps (NETs) production in neutrophils with and without ETI treatment.
Main Results:
- Neutrophils express functional CFTR, and ETI treatment influences its subcellular localization in CF neutrophils.
- ETI treatment reduced intracellular chloride levels in human neutrophils, indicating CFTR-dependent chloride efflux.
- ETI treatment potentiated NADPH oxidase activity, enhanced NETs production, and restored intracellular antimicrobial killing in CF neutrophils.
Conclusions:
- CFTR plays a critical role in regulating neutrophil functions.
- CFTR modulators like ETI can restore the antimicrobial capabilities of neutrophils from people with CF.
- These findings highlight a novel mechanism for CFTR modulator therapy beyond correcting CFTR protein function.
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