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Structure-Function Relationships Of Mucociliary Clearance In Human Airways
Preprint   Open access

Structure-Function Relationships Of Mucociliary Clearance In Human Airways

Amy Ryan, Doris Roth, Ayse Tugce Sahin, Feng Ling, Christiana Senger, Erik Quiroz, Ben Calvert, Anne van der Does, Tankut Güney, Annemarie van Schadewijk, …
Research square
04/25/2024
DOI: 10.21203/rs.3.rs-4164522/v1
PMCID: PMC11092836
PMID: 38746209
url
https://doi.org/10.21203/rs.3.rs-4164522/v1View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Our study focuses on the intricate connection between tissue-level organization and ciliated organ function in humans, particularly in understanding the morphological organization of airways and their role in mucociliary clearance. Mucociliary clearance is a key mechanical defense mechanism of human airways, and clearance failure is associated with many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. While single-cell transcriptomics have unveiled the cellular complexity of the human airway epithelium, our understanding of the mechanics that link epithelial structure to clearance function mainly stem from animal models. This reliance on animal data limits crucial insights into human airway barrier function and hampers the human-relevant modeling of airway diseases. This study, for the first time, maps the distribution of ciliated and secretory cell types along the airway tree in both rats and humans, noting species-specific differences in ciliary function and elucidates structural parameters of airway epithelia that predict clearance function in both native and tissues alike. By uncovering how tissue organization influences ciliary function, we can better understand disruptions in mucociliary clearance, which could have implications for various ciliated organs beyond the airways.

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