Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection

Autores
Brazee, Patricia L.; Morales Nebreda, Luisa; Magnani, Natalia Daniela; Garcia, Joe G. N.; Misharin, Alexander V.; Ridge, Karen M.; Budinger, G.R. Scott; Iwai, Kazuhiro; Dada, Laura Andrea; Sznajder, Jacob I.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Influenza A virus (IAV) is among the most common causes of pneumonia-related death worldwide. Pulmonary epithelial cells are the primary target for viral infection and replication and respond by releasing inflammatory mediators that recruit immune cells to mount the host response. Severe lung injury and death during IAV infection result from an exuberant host inflammatory response. The linear ubiquitin assembly complex (LUBAC), composed of SHARPIN, HOIL-1L, and HOIP, is a critical regulator of NF-κB–dependent inflammation. Using mice with lung epithelial–specific deletions of HOIL-1L or HOIP in a model of IAV infection, we provided evidence that, while a reduction in the inflammatory response was beneficial, ablation of the LUBAC-dependent lung epithelial–driven response worsened lung injury and increased mortality. Moreover, we described a mechanism for the upregulation of HOIL-1L in infected and noninfected cells triggered by the activation of type I IFN receptor and mediated by IRF1, which was maladaptive and contributed to hyperinflammation. Thus, we propose that lung epithelial LUBAC acts as a molecular rheostat that could be selectively targeted to modulate the immune response in patients with severe IAV-induced pneumonia.
Fil: Brazee, Patricia L.. Northwestern University; Estados Unidos
Fil: Morales Nebreda, Luisa. Northwestern University; Estados Unidos
Fil: Magnani, Natalia Daniela. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Garcia, Joe G. N.. University of Arizona; Estados Unidos
Fil: Misharin, Alexander V.. Northwestern University; Estados Unidos
Fil: Ridge, Karen M.. Northwestern University; Estados Unidos
Fil: Budinger, G.R. Scott. Northwestern University; Estados Unidos
Fil: Iwai, Kazuhiro. Kyoto University; Japón
Fil: Dada, Laura Andrea. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Sznajder, Jacob I.. Northwestern University; Estados Unidos
Materia
LINEAR UBIQUITIN ASSEMBLY COMPLEX
INFLUENZA
LUNG EPITHELIUM
INFLAMMATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/124532
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/124532
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infectionBrazee, Patricia L.Morales Nebreda, LuisaMagnani, Natalia DanielaGarcia, Joe G. N.Misharin, Alexander V.Ridge, Karen M.Budinger, G.R. ScottIwai, KazuhiroDada, Laura AndreaSznajder, Jacob I.LINEAR UBIQUITIN ASSEMBLY COMPLEXINFLUENZALUNG EPITHELIUMINFLAMMATIONhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Influenza A virus (IAV) is among the most common causes of pneumonia-related death worldwide. Pulmonary epithelial cells are the primary target for viral infection and replication and respond by releasing inflammatory mediators that recruit immune cells to mount the host response. Severe lung injury and death during IAV infection result from an exuberant host inflammatory response. The linear ubiquitin assembly complex (LUBAC), composed of SHARPIN, HOIL-1L, and HOIP, is a critical regulator of NF-κB–dependent inflammation. Using mice with lung epithelial–specific deletions of HOIL-1L or HOIP in a model of IAV infection, we provided evidence that, while a reduction in the inflammatory response was beneficial, ablation of the LUBAC-dependent lung epithelial–driven response worsened lung injury and increased mortality. Moreover, we described a mechanism for the upregulation of HOIL-1L in infected and noninfected cells triggered by the activation of type I IFN receptor and mediated by IRF1, which was maladaptive and contributed to hyperinflammation. Thus, we propose that lung epithelial LUBAC acts as a molecular rheostat that could be selectively targeted to modulate the immune response in patients with severe IAV-induced pneumonia.Fil: Brazee, Patricia L.. Northwestern University; Estados UnidosFil: Morales Nebreda, Luisa. Northwestern University; Estados UnidosFil: Magnani, Natalia Daniela. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Garcia, Joe G. N.. University of Arizona; Estados UnidosFil: Misharin, Alexander V.. Northwestern University; Estados UnidosFil: Ridge, Karen M.. Northwestern University; Estados UnidosFil: Budinger, G.R. Scott. Northwestern University; Estados UnidosFil: Iwai, Kazuhiro. Kyoto University; JapónFil: Dada, Laura Andrea. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Sznajder, Jacob I.. Northwestern University; Estados UnidosAmerican Society for Clinical Investigation2019-11-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/124532Brazee, Patricia L.; Morales Nebreda, Luisa; Magnani, Natalia Daniela; Garcia, Joe G. N.; Misharin, Alexander V.; et al.; Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection; American Society for Clinical Investigation; Journal of Clinical Investigation; 130; 3; 12-11-2019; 1301-13141558-8238CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jci.org/articles/view/128368info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI128368info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:35:22Zoai:ri.conicet.gov.ar:11336/124532instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:35:22.822CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
title Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
spellingShingle Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
Brazee, Patricia L.
LINEAR UBIQUITIN ASSEMBLY COMPLEX
INFLUENZA
LUNG EPITHELIUM
INFLAMMATION
title_short Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
title_full Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
title_fullStr Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
title_full_unstemmed Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
title_sort Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection
dc.creator.none.fl_str_mv Brazee, Patricia L.
Morales Nebreda, Luisa
Magnani, Natalia Daniela
Garcia, Joe G. N.
Misharin, Alexander V.
Ridge, Karen M.
Budinger, G.R. Scott
Iwai, Kazuhiro
Dada, Laura Andrea
Sznajder, Jacob I.
author Brazee, Patricia L.
author_facet Brazee, Patricia L.
Morales Nebreda, Luisa
Magnani, Natalia Daniela
Garcia, Joe G. N.
Misharin, Alexander V.
Ridge, Karen M.
Budinger, G.R. Scott
Iwai, Kazuhiro
Dada, Laura Andrea
Sznajder, Jacob I.
author_role author
author2 Morales Nebreda, Luisa
Magnani, Natalia Daniela
Garcia, Joe G. N.
Misharin, Alexander V.
Ridge, Karen M.
Budinger, G.R. Scott
Iwai, Kazuhiro
Dada, Laura Andrea
Sznajder, Jacob I.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LINEAR UBIQUITIN ASSEMBLY COMPLEX
INFLUENZA
LUNG EPITHELIUM
INFLAMMATION
topic LINEAR UBIQUITIN ASSEMBLY COMPLEX
INFLUENZA
LUNG EPITHELIUM
INFLAMMATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Influenza A virus (IAV) is among the most common causes of pneumonia-related death worldwide. Pulmonary epithelial cells are the primary target for viral infection and replication and respond by releasing inflammatory mediators that recruit immune cells to mount the host response. Severe lung injury and death during IAV infection result from an exuberant host inflammatory response. The linear ubiquitin assembly complex (LUBAC), composed of SHARPIN, HOIL-1L, and HOIP, is a critical regulator of NF-κB–dependent inflammation. Using mice with lung epithelial–specific deletions of HOIL-1L or HOIP in a model of IAV infection, we provided evidence that, while a reduction in the inflammatory response was beneficial, ablation of the LUBAC-dependent lung epithelial–driven response worsened lung injury and increased mortality. Moreover, we described a mechanism for the upregulation of HOIL-1L in infected and noninfected cells triggered by the activation of type I IFN receptor and mediated by IRF1, which was maladaptive and contributed to hyperinflammation. Thus, we propose that lung epithelial LUBAC acts as a molecular rheostat that could be selectively targeted to modulate the immune response in patients with severe IAV-induced pneumonia.
Fil: Brazee, Patricia L.. Northwestern University; Estados Unidos
Fil: Morales Nebreda, Luisa. Northwestern University; Estados Unidos
Fil: Magnani, Natalia Daniela. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Garcia, Joe G. N.. University of Arizona; Estados Unidos
Fil: Misharin, Alexander V.. Northwestern University; Estados Unidos
Fil: Ridge, Karen M.. Northwestern University; Estados Unidos
Fil: Budinger, G.R. Scott. Northwestern University; Estados Unidos
Fil: Iwai, Kazuhiro. Kyoto University; Japón
Fil: Dada, Laura Andrea. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Sznajder, Jacob I.. Northwestern University; Estados Unidos
description Influenza A virus (IAV) is among the most common causes of pneumonia-related death worldwide. Pulmonary epithelial cells are the primary target for viral infection and replication and respond by releasing inflammatory mediators that recruit immune cells to mount the host response. Severe lung injury and death during IAV infection result from an exuberant host inflammatory response. The linear ubiquitin assembly complex (LUBAC), composed of SHARPIN, HOIL-1L, and HOIP, is a critical regulator of NF-κB–dependent inflammation. Using mice with lung epithelial–specific deletions of HOIL-1L or HOIP in a model of IAV infection, we provided evidence that, while a reduction in the inflammatory response was beneficial, ablation of the LUBAC-dependent lung epithelial–driven response worsened lung injury and increased mortality. Moreover, we described a mechanism for the upregulation of HOIL-1L in infected and noninfected cells triggered by the activation of type I IFN receptor and mediated by IRF1, which was maladaptive and contributed to hyperinflammation. Thus, we propose that lung epithelial LUBAC acts as a molecular rheostat that could be selectively targeted to modulate the immune response in patients with severe IAV-induced pneumonia.
publishDate 2019
dc.date.none.fl_str_mv 2019-11-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/124532
Brazee, Patricia L.; Morales Nebreda, Luisa; Magnani, Natalia Daniela; Garcia, Joe G. N.; Misharin, Alexander V.; et al.; Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection; American Society for Clinical Investigation; Journal of Clinical Investigation; 130; 3; 12-11-2019; 1301-1314
1558-8238
CONICET Digital
CONICET
url http://hdl.handle.net/11336/124532
identifier_str_mv Brazee, Patricia L.; Morales Nebreda, Luisa; Magnani, Natalia Daniela; Garcia, Joe G. N.; Misharin, Alexander V.; et al.; Linear ubiquitin assembly complex regulates lung epithelial–driven responses during influenza infection; American Society for Clinical Investigation; Journal of Clinical Investigation; 130; 3; 12-11-2019; 1301-1314
1558-8238
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jci.org/articles/view/128368
info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI128368
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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 reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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