AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity

Autores
Schmid, Edward T.; Pang, Iris K.; Carrera Silva, Eugenio Antonio; Bosurgi, Lidia; Miner, Jonathan J; Diamond, Michael S; Iwasaki, Akiko; Rothlin, Carla
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl(-/-) dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl(-/-) mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl(-/-) mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.
Fil: Schmid, Edward T.. University of Yale; Estados Unidos
Fil: Pang, Iris K.. University of Yale; Estados Unidos
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos
Fil: Bosurgi, Lidia. University of Yale; Estados Unidos
Fil: Miner, Jonathan J. Washington University School of Medicine; Estados Unidos
Fil: Diamond, Michael S. Washington University School of Medicine; Estados Unidos
Fil: Iwasaki, Akiko. University of Yale; Estados Unidos
Fil: Rothlin, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos
Materia
AXL
DENDRITIC CELLS
ANTIVIRAL RESPONSE
T CELL
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:11336/53313
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/53313
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling AXL receptor tyrosine kinase is required for T cell priming and antiviral immunitySchmid, Edward T.Pang, Iris K.Carrera Silva, Eugenio AntonioBosurgi, LidiaMiner, Jonathan JDiamond, Michael SIwasaki, AkikoRothlin, CarlaAXLDENDRITIC CELLSANTIVIRAL RESPONSET CELLhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl(-/-) dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl(-/-) mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl(-/-) mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.Fil: Schmid, Edward T.. University of Yale; Estados UnidosFil: Pang, Iris K.. University of Yale; Estados UnidosFil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados UnidosFil: Bosurgi, Lidia. University of Yale; Estados UnidosFil: Miner, Jonathan J. Washington University School of Medicine; Estados UnidosFil: Diamond, Michael S. Washington University School of Medicine; Estados UnidosFil: Iwasaki, Akiko. University of Yale; Estados UnidosFil: Rothlin, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados UnidoseLife Sciences Publications2016-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53313Schmid, Edward T.; Pang, Iris K.; Carrera Silva, Eugenio Antonio; Bosurgi, Lidia; Miner, Jonathan J; et al.; AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity; eLife Sciences Publications; eLife; 5; 6-2016; 1-182050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.12414info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/12414info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:06Zoai:ri.conicet.gov.ar:11336/53313instacron: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 09:44:06.873CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
title AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
spellingShingle AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
Schmid, Edward T.
AXL
DENDRITIC CELLS
ANTIVIRAL RESPONSE
T CELL
title_short AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
title_full AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
title_fullStr AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
title_full_unstemmed AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
title_sort AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
dc.creator.none.fl_str_mv Schmid, Edward T.
Pang, Iris K.
Carrera Silva, Eugenio Antonio
Bosurgi, Lidia
Miner, Jonathan J
Diamond, Michael S
Iwasaki, Akiko
Rothlin, Carla
author Schmid, Edward T.
author_facet Schmid, Edward T.
Pang, Iris K.
Carrera Silva, Eugenio Antonio
Bosurgi, Lidia
Miner, Jonathan J
Diamond, Michael S
Iwasaki, Akiko
Rothlin, Carla
author_role author
author2 Pang, Iris K.
Carrera Silva, Eugenio Antonio
Bosurgi, Lidia
Miner, Jonathan J
Diamond, Michael S
Iwasaki, Akiko
Rothlin, Carla
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AXL
DENDRITIC CELLS
ANTIVIRAL RESPONSE
T CELL
topic AXL
DENDRITIC CELLS
ANTIVIRAL RESPONSE
T CELL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl(-/-) dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl(-/-) mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl(-/-) mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.
Fil: Schmid, Edward T.. University of Yale; Estados Unidos
Fil: Pang, Iris K.. University of Yale; Estados Unidos
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos
Fil: Bosurgi, Lidia. University of Yale; Estados Unidos
Fil: Miner, Jonathan J. Washington University School of Medicine; Estados Unidos
Fil: Diamond, Michael S. Washington University School of Medicine; Estados Unidos
Fil: Iwasaki, Akiko. University of Yale; Estados Unidos
Fil: Rothlin, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos
description The receptor tyrosine kinase (RTK) AXL is induced in response to type I interferons (IFNs) and limits their production through a negative feedback loop. Enhanced production of type I IFNs in Axl(-/-) dendritic cells (DCs) in vitro have led to speculation that inhibition of AXL would promote antiviral responses. Notwithstanding, type I IFNs also exert potent immunosuppressive functions. Here we demonstrate that ablation of AXL enhances the susceptibility to infection by influenza A virus and West Nile virus. The increased type I IFN response in Axl(-/-) mice was associated with diminished DC maturation, reduced production of IL-1β, and defective antiviral T cell immunity. Blockade of type I IFN receptor or administration of IL-1β to Axl(-/-) mice restored the antiviral adaptive response and control of infection. Our results demonstrate that AXL is essential for limiting the immunosuppressive effects of type I IFNs and enabling the induction of protective antiviral adaptive immunity.
publishDate 2016
dc.date.none.fl_str_mv 2016-06
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/11336/53313
Schmid, Edward T.; Pang, Iris K.; Carrera Silva, Eugenio Antonio; Bosurgi, Lidia; Miner, Jonathan J; et al.; AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity; eLife Sciences Publications; eLife; 5; 6-2016; 1-18
2050-084X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53313
identifier_str_mv Schmid, Edward T.; Pang, Iris K.; Carrera Silva, Eugenio Antonio; Bosurgi, Lidia; Miner, Jonathan J; et al.; AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity; eLife Sciences Publications; eLife; 5; 6-2016; 1-18
2050-084X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.12414
info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/12414
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 eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
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
_version_ 1844613388033851392
score 13.070432

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