Related Experiment Video
Updated: May 7, 2026

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
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.
Abstract:
Cystic fibrosis (CF) is a common genetic disease caused by a defective CF-transmembrane conductance regulator (CFTR). People with CF (pwCF) are prone to develop infections by opportunistic pathogens, including Burkholderia cenocepacia, leading to chronic inflammation. Neutrophils release granular proteins and oxidative products that contribute to tissue damage. CFTR modulators are a new treatment for pwCF aiming to correct the subcellular location and function of the CFTR ion channel. The triple modulator combination of Elexacaftor, Tezacaftor, and Ivacaftor (ETI) or Trikafta® has significantly improved clinical symptoms and overall provided a better quality of life for pwCF. The mechanism by which CFTR modulators help to restore the antimicrobial functions of neutrophils is unknown. The present study demonstrated that neutrophils functionally express CFTR and revealed how ETI modifies subcellular CFTR trafficking in CF neutrophils. In addition, ETI treatment reduced intracellular chloride levels in human neutrophils, indicating activation of CFTR-dependent chloride efflux. Finally, ETI treatment also re-established the intracellular antimicrobial killing of CF neutrophils by potentiating NADPH oxidase activity and improved trapping microbes by enhancing the production of Neutrophil Extracellular Traps (NETs). Together, our findings suggest that CFTR has an essential role in controlling neutrophil functions and CFTR modulators help restore the antimicrobial functions of neutrophils from pwCF.
More Related Videos
Related Concept Videos
Cystic Fibrosis: Management
Sinus disease and chronic...
Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
Drugs Used in Lower Respiratory Disorders: Overview
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...
COPD: Management Using Bronchodilators and Corticosteroids
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

