Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death.
AT1 cell depletion
cell death
iDTR
lung injury
sterile inflammation
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
19
07
2023
accepted:
11
09
2023
medline:
23
10
2023
pubmed:
16
10
2023
entrez:
16
10
2023
Statut:
epublish
Résumé
The pathogenesis of chronic lung diseases is multifaceted with a major role of recurrent micro-injuries of the epithelium. While several reports clearly indicated a prominent role for surfactant-producing alveolar epithelial type 2 (AT2) cells, the contribution of gas exchange-permissive alveolar epithelial type 1 (AT1) cells has not been addressed yet. Here, we investigated whether repeated injury of AT1 cells leads to inflammation and interstitial fibrosis. We chose an inducible model of AT1 cell depletion following local diphtheria toxin (DT) administration using an iDTR flox/flox (idTR We investigated repeated doses and intervals of DT to induce cell death of AT1 cells causing inflammation and interstitial fibrosis. We found that repeated DT administrations at 1ng in iDTR Together, we demonstrate that depletion of AT1 cells using repeated injury represents a novel approach to investigate chronic lung inflammatory diseases and to identify new therapeutic targets.
Identifiants
pubmed: 37841243
doi: 10.3389/fimmu.2023.1261483
pmc: PMC10568624
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1261483Informations de copyright
Copyright © 2023 Carignon, De Moura Rodrigues, Gosset, Culerier, Huot-Marchand, Savigny, Kaya, Quesniaux, Gombault, Couillin, Ryffel, Le Bert and Riteau.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision
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