Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death
IntroductionThe 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1261483/full |
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| author | Sandra Carignon Dorian De Moura Rodrigues David Gosset Elodie Culerier Sarah Huot-Marchand Florence Savigny Eric Kaya Valerie Quesniaux Aurélie Gombault Isabelle Couillin Bernhard Ryffel Marc Le Bert Nicolas Riteau |
| author_facet | Sandra Carignon Dorian De Moura Rodrigues David Gosset Elodie Culerier Sarah Huot-Marchand Florence Savigny Eric Kaya Valerie Quesniaux Aurélie Gombault Isabelle Couillin Bernhard Ryffel Marc Le Bert Nicolas Riteau |
| author_sort | Sandra Carignon |
| collection | DOAJ |
| description | IntroductionThe 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.MethodsWe chose an inducible model of AT1 cell depletion following local diphtheria toxin (DT) administration using an iDTR flox/flox (idTRfl/fl) X Aquaporin 5CRE (Aqp5CRE) transgenic mouse strain.ResultsWe 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 iDTRfl/fl X Aqp5CRE mice cause AT1 cell death leading to inflammation, increased tissue repair markers and interstitial pulmonary fibrosis.DiscussionTogether, 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. |
| first_indexed | 2024-03-11T21:15:58Z |
| format | Article |
| id | doaj.art-71754b8105ab4c509c24ac5dfc6cb235 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T21:15:58Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-71754b8105ab4c509c24ac5dfc6cb2352023-09-29T04:06:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12614831261483Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell deathSandra Carignon0Dorian De Moura Rodrigues1David Gosset2Elodie Culerier3Sarah Huot-Marchand4Florence Savigny5Eric Kaya6Valerie Quesniaux7Aurélie Gombault8Isabelle Couillin9Bernhard Ryffel10Marc Le Bert11Nicolas Riteau12University of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceCenter for Molecular Biophysics, CNRS Unité propre de recherche 4301, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceUniversity of Orleans and CNRS, Immunologie et Neurogénétique Expérimentales et Moléculaires -UMR7355, Orleans, FranceIntroductionThe 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.MethodsWe chose an inducible model of AT1 cell depletion following local diphtheria toxin (DT) administration using an iDTR flox/flox (idTRfl/fl) X Aquaporin 5CRE (Aqp5CRE) transgenic mouse strain.ResultsWe 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 iDTRfl/fl X Aqp5CRE mice cause AT1 cell death leading to inflammation, increased tissue repair markers and interstitial pulmonary fibrosis.DiscussionTogether, 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1261483/fullAT1 cell depletionsterile inflammationlung injuryiDTRcell death |
| spellingShingle | Sandra Carignon Dorian De Moura Rodrigues David Gosset Elodie Culerier Sarah Huot-Marchand Florence Savigny Eric Kaya Valerie Quesniaux Aurélie Gombault Isabelle Couillin Bernhard Ryffel Marc Le Bert Nicolas Riteau Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death Frontiers in Immunology AT1 cell depletion sterile inflammation lung injury iDTR cell death |
| title | Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death |
| title_full | Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death |
| title_fullStr | Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death |
| title_full_unstemmed | Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death |
| title_short | Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death |
| title_sort | lung inflammation and interstitial fibrosis by targeted alveolar epithelial type i cell death |
| topic | AT1 cell depletion sterile inflammation lung injury iDTR cell death |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1261483/full |
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