Pulmonary ionocyte

Pulmonary ionocytes are a rare (~1%) specialized epithelial cell type in the respiratory tract, discovered in 2018, that express the highest levels of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein (Nature, 2018). They play a critical role in regulating the pH and volume of the airway surface liquid (ASL) through the transport of chloride and bicarbonate ions (JCI, 2024). In diseases like cystic fibrosis, the dysfunction or loss of these cells leads to dehydrated, acidic mucus and impaired mucociliary clearance (ATS Journals, 2022). They are considered a promising target for next-generation therapies, including gene editing and cell replacement, as well as cell-specific pharmacological modulation via targets like PDE1C (Children's Hospital Boston, 2023). Recent studies also suggest their involvement in non-eosinophilic asthma, where inflammation-induced loss of ionocytes may exacerbate disease (Respirology, 2025). While not a single molecule or receptor, these cells represent a novel cellular target for precision medicine in muco-obstructive lung diseases.

Other names

Airway ionocyteFoxi1-positive pulmonary ionocyteCFTR-rich ionocyte

CFTR modulation (correction and potentiation), PDE1C inhibition to increase cAMP-mediated CFTR activity, and potential gene or cell therapy to restore CFTR function in these cells.