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[Preprint]. 2025 Mar 26:2025.03.25.645303.
doi: 10.1101/2025.03.25.645303.

CFTR function in alveolar type 1 cells drives lung liquid secretion and host defense

Sayahi Suthakaran, Sonya Homami, Deebly Chavez, Stephanie Tang, Sarah K L Moore, Chaya Sussman, Jimmy Zhang, Clemente J Britto, Alice Prince, Alison J May, Jaymin J Kathiriya, Jaime L Hook

CFTR function in alveolar type 1 cells drives lung liquid secretion and host defense

Sayahi Suthakaran et al. bioRxiv. .

Abstract

Loss of the liquid layer that lines the lung's air-facing surface underpins mechanisms of major lung diseases, but the development of therapies that restore liquid secretion is hampered by an incomplete understanding of the cell types that drive it. Here, we show CFTR function in alveolar type 1 (AT1) cells - a cell type that comprises 95% of the lung surface but is presumed to be unimportant in CFTR-related diseases - is critical to lung liquid secretion and the secretion-mediated clearance of particles and S. aureus from lung alveoli. Our findings reveal essential roles for AT1 cells in lung homeostasis and defense, and they call for a reevaluation of the role of AT1 cells in CFTR-related diseases. We suggest AT1 cells be considered key targets of secretion-restoring therapies.

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