# Bronchial smooth muscle extracellular vesicles interfere with bronchial epithelium metabolism and function in asthma

## TL;DR

Asthmatic bronchial smooth muscle cells release more extracellular vesicles, which alter epithelial cell metabolism, weaken their barrier function, and increase rhinovirus infection.

## Contribution

This study is the first to show that BSM-derived EVs in asthma affect bronchial epithelium metabolism and function.

## Key findings

- Asthmatic BSM cells produce more EVs containing bioenergetic metabolites.
- EVs from asthmatic BSM cells disrupt bronchial epithelium barrier function and increase ATP production.
- BSM-derived EVs enhance rhinovirus replication in bronchial epithelium.

## Abstract

Bronchial smooth muscle (BSM) remodeling is an important feature of severe asthma pathophysiology. We previously showed that asthmatic BSM is metabolically different and increased rhinovirus (RV) replication rate, the main trigger of severe asthma exacerbations. Extracellular vesicles (EVs) are the key mediator in cell-cell communication, but the role of BSM cells-derived EVs on bronchial epithelial has never been investigated in asthma. Using severe asthmatic and non-asthmatic tissue collection, we show that asthmatic BSM cells are able to produce a greater amount of EVs containing metabolites involved in bioenergetics. We study the bronchial epithelium energetic rewiring following stimulation with asthmatic BSM cells-derived EVs. Modifications of bronchial epithelium metabolic behavior were associated with an increased ATP production and a breakdown of bronchial epithelium barrier function such as ciliary beating frequency and efficiency. Finally, we show that asthmatic BSM cells-derived EVs increased RV replication in bronchial epithelium following RV infection.

•Asthmatic BSM cells produce an increased number of extracellular vesicles (EVs)•Asthmatic BSM cells-derived EVs rewire cellular energetic metabolism of bronchial epithelium•Metabolic modifications are associated to a decreased barrier function•Asthmatic BSM cells-derived EVs increase rhinovirus infection

Asthmatic BSM cells produce an increased number of extracellular vesicles (EVs)

Asthmatic BSM cells-derived EVs rewire cellular energetic metabolism of bronchial epithelium

Metabolic modifications are associated to a decreased barrier function

Asthmatic BSM cells-derived EVs increase rhinovirus infection

Pathology; Cell biology