Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease

Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL act...

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Autores: Borchers, Michael T., Wesselkamper. SCcott C., Curull, Victor, Ramirez Sarmiento, Alba, Sánchez Font, Albert, García Aymerich, Judith, Coronell, Carlos, Lloreta Trull, Josep, Agustí García-Navarro, Àlvar, Gea Guiral, Joaquim, Howington, John A., Reed, Michael F., Starnes, Sandra L., Harris, Nathaniel L., Vitucci, Mark, Eppert, Bryan L., Motz, Gregory T., Fogel, Kevin, McGraw, Dennis W., Tiichelaar, Jay W., Orozco-Levi, Mauricio
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/48195
Acesso em linha:https://hdl.handle.net/2445/48195
Access Level:acceso abierto
Palavra-chave:Malalties pulmonars obstructives cròniques
Malalties de l'aparell respiratori
Assaigs clínics
Chronic obstructive pulmonary diseases
Clinical trials
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spelling Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like diseaseBorchers, Michael T.Wesselkamper. SCcott C.Curull, VictorRamirez Sarmiento, AlbaSánchez Font, AlbertGarcía Aymerich, JudithCoronell, CarlosLloreta Trull, JosepAgustí García-Navarro, ÀlvarGea Guiral, JoaquimHowington, John A.Reed, Michael F.Starnes, Sandra L.Harris, Nathaniel L.Vitucci, MarkEppert, Bryan L.Motz, Gregory T.Fogel, KevinMcGraw, Dennis W.Tiichelaar, Jay W.Orozco-Levi, MauricioMalalties pulmonars obstructives cròniquesMalalties de l'aparell respiratoriAssaigs clínicsChronic obstructive pulmonary diseasesMalalties de l'aparell respiratoriClinical trialsChronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early tran - script 1 (RAET1)as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies.American Society for Clinical Investigation2009info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/48195Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1172/JC1344Journal of Clinical Investigation, 2009, vol. 119, num. 3, p. 636-649http://dx.doi.org/10.1172/JC1344(c) American Society for Clinical Investigation, 2009info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/481952026-05-27T06:46:51Z
dc.title.none.fl_str_mv Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
title Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
spellingShingle Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
Borchers, Michael T.
Malalties pulmonars obstructives cròniques
Malalties de l'aparell respiratori
Assaigs clínics
Chronic obstructive pulmonary diseases
Malalties de l'aparell respiratori
Clinical trials
title_short Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
title_full Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
title_fullStr Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
title_full_unstemmed Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
title_sort Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease
dc.creator.none.fl_str_mv Borchers, Michael T.
Wesselkamper. SCcott C.
Curull, Victor
Ramirez Sarmiento, Alba
Sánchez Font, Albert
García Aymerich, Judith
Coronell, Carlos
Lloreta Trull, Josep
Agustí García-Navarro, Àlvar
Gea Guiral, Joaquim
Howington, John A.
Reed, Michael F.
Starnes, Sandra L.
Harris, Nathaniel L.
Vitucci, Mark
Eppert, Bryan L.
Motz, Gregory T.
Fogel, Kevin
McGraw, Dennis W.
Tiichelaar, Jay W.
Orozco-Levi, Mauricio
author Borchers, Michael T.
author_facet Borchers, Michael T.
Wesselkamper. SCcott C.
Curull, Victor
Ramirez Sarmiento, Alba
Sánchez Font, Albert
García Aymerich, Judith
Coronell, Carlos
Lloreta Trull, Josep
Agustí García-Navarro, Àlvar
Gea Guiral, Joaquim
Howington, John A.
Reed, Michael F.
Starnes, Sandra L.
Harris, Nathaniel L.
Vitucci, Mark
Eppert, Bryan L.
Motz, Gregory T.
Fogel, Kevin
McGraw, Dennis W.
Tiichelaar, Jay W.
Orozco-Levi, Mauricio
author_role author
author2 Wesselkamper. SCcott C.
Curull, Victor
Ramirez Sarmiento, Alba
Sánchez Font, Albert
García Aymerich, Judith
Coronell, Carlos
Lloreta Trull, Josep
Agustí García-Navarro, Àlvar
Gea Guiral, Joaquim
Howington, John A.
Reed, Michael F.
Starnes, Sandra L.
Harris, Nathaniel L.
Vitucci, Mark
Eppert, Bryan L.
Motz, Gregory T.
Fogel, Kevin
McGraw, Dennis W.
Tiichelaar, Jay W.
Orozco-Levi, Mauricio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties pulmonars obstructives cròniques
Malalties de l'aparell respiratori
Assaigs clínics
Chronic obstructive pulmonary diseases
Malalties de l'aparell respiratori
Clinical trials
topic Malalties pulmonars obstructives cròniques
Malalties de l'aparell respiratori
Assaigs clínics
Chronic obstructive pulmonary diseases
Malalties de l'aparell respiratori
Clinical trials
description Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early tran - script 1 (RAET1)as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies.
publishDate 2009
dc.date.none.fl_str_mv 2009
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/48195
url https://hdl.handle.net/2445/48195
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1172/JC1344
Journal of Clinical Investigation, 2009, vol. 119, num. 3, p. 636-649
http://dx.doi.org/10.1172/JC1344
dc.rights.none.fl_str_mv (c) American Society for Clinical Investigation, 2009
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Clinical Investigation, 2009
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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