# STRUCTURE-FUNCTION RELATIONSHIPS OF MUCOCILIARY CLEARANCE IN HUMAN AIRWAYS

## TL;DR

This study explores how the structure of human airway tissues affects mucociliary clearance, a key defense mechanism against respiratory diseases.

## Contribution

The study provides the first comparative mapping of ciliated and secretory cells in human and rat airways, revealing species-specific differences and structural predictors of clearance function.

## Key findings

- Ciliated and secretory cell distributions vary along the human and rat airway trees.
- Structural parameters of epithelia predict mucociliary clearance function in native and in vitro tissues.
- Species-specific differences in ciliary function were identified, impacting human-relevant disease modeling.

## 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 in vitro 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 in vitro 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.