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
iScience. 2025-06-01; 28(6): 112546
DOI: 10.1016/j.isci.2025.112546

Celle E(1)(2), Chahin A(1)(2), Beaufils F(1)(2)(3), Cardouat G(1)(2), Eyraud
E(1)(2), Bouchet C(1)(2), Campagnac M(1)(2), Ousova O(1)(2), Begueret H(3),
Thumerel M(1)(2)(3), Dubois R(1), Dupuy JW(1)(2)(4), Leste-Lasserre T(1)(2),
Lacomme S(1)(2)(4), Lager-Lachaud N(5), Bellvert F(5), Marthan R(1)(2)(3),
Girodet PO(1)(2)(3), Berger P(1)(2)(3), Trian T(1)(2), Esteves P(1)(2).

Author information:
(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.

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.

DOI: 10.1016/j.isci.2025.112546
PMCID: PMC12141081
PMID: 40487443

Conflict of interest statement: The authors declare no competing interests.