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

Elisa Celle; Amine Chahin; Fabien Beaufils; Guillaume Cardouat; Edmée Eyraud; Clément Bouchet; Marilyne Campagnac; Olga Ousova; Hugues Begueret; Matthieu Thumerel; Rémi Dubois; Jean-William Dupuy; Thierry Leste-Lasserre; Sabrina Lacomme; Nina Lager-Lachaud; Floriant Bellvert; Roger Marthan; Pierre-Olivier Girodet; Patrick Berger; Thomas Trian; Pauline Esteves

doi:10.1016/j.isci.2025.112546

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

iScience. 2025 Apr 29;28(6):112546. doi: 10.1016/j.isci.2025.112546. eCollection 2025 Jun 20.

Authors

Elisa Celle^{1

2}, Amine Chahin^{1

2}, Fabien Beaufils^{1

2

3}, Guillaume Cardouat^{1

2}, Edmée Eyraud^{1

2}, Clément Bouchet^{1

2}, Marilyne Campagnac^{1

2}, Olga Ousova^{1

2}, Hugues Begueret³, Matthieu Thumerel^{1

2

3}, Rémi Dubois¹, Jean-William Dupuy^{1

2

4}, Thierry Leste-Lasserre^{1

2}, Sabrina Lacomme^{1

2

4}, Nina Lager-Lachaud⁵, Floriant Bellvert⁵, Roger Marthan^{1

2

3}, Pierre-Olivier Girodet^{1

2

3}, Patrick Berger^{1

2

3}, Thomas Trian^{1

2}, Pauline Esteves^{1

2}

Affiliations

¹ Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux Proteome, TBM-Core, US5, UAR 3427, OncoProt, CIC 1401, 33000 Bordeaux, France.
² INSERM, Centre de Recherche Cardio-thoracique de Bordeaux U1045, Plateforme Transcriptome Neurocentre Magendie U1215, TBM-Core, US5, UAR 3427, OncoProt, BIC, UAR 3420, 33000 Bordeaux, France.
³ CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pharmacologie, CIC 1401, Service de chirurgie thoracique, 33604 Pessac, France.
⁴ CNRS, TBM-Core, US5, UAR 3427, OncoProt, BIC, UAR 3420, 33000 Bordeaux, France.
⁵ Université de Toulouse, CNRS 5504, INRA 792, INSA Toulouse, Toulouse Biotechnology Institute, Bio & Chemical Engineering, MetaToul, Toulouse, France.

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.

Keywords: Cell biology; Pathology.