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dc.contributor.authorMontes-Casado, Maria 
dc.contributor.authorOjeda, Gloria 
dc.contributor.authorAragoneses-Fenoll, Laura 
dc.contributor.authorLopez, Daniel 
dc.contributor.authorAndres, Belen de 
dc.contributor.authorGaspar, Maria Luisa 
dc.contributor.authorDianzani, Umberto
dc.contributor.authorRojo, José M
dc.contributor.authorPortoles, Pilar 
dc.date.accessioned2019-11-25T12:58:14Z
dc.date.available2019-11-25T12:58:14Z
dc.date.issued2019
dc.identifier.citationPLoS One. 2019 Jul 8;14(7):e0219449.es_ES
dc.identifier.issn1932-6203es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8704
dc.description.abstractSignaling through the inducible costimulator ICOS is required for the homeostasis and function of various immune cell populations, with an outstanding role in the generation and maintenance of germinal centers. Very recently, it has been suggested that the clinical phenotype of ICOS-deficient patients is much broader than initially anticipated and the innate immune response might be also affected. However, the role of the ICOS/ICOS-Ligand axis in the homeostasis and development of innate NK cells is not known, and reports on its participation in NK cell activation are scarce. NK cells may express low levels of ICOS that are markedly enhanced upon activation. We show here that ICOS-deficient (ICOS-KO) mice present low NK cell numbers and defects in the homeostasis of these cells, with delayed maturation and altered expression of the developmental NK cell markers CD122, NK1.1, CD11b or CD27. Our experiments in mixed bone marrow chimera mice indicate that, both, cell-intrinsic defects of ICOS-KO NK and deficiencies in the milieu of these mice contribute to the altered phenotype. ICOS-deficient NK cells show impaired production of IFN-γ and cytotoxicity, and a final outcome of defects in NK cell-mediated effector function during the response to poly(I:C) or vaccinia virus infection in vivo. Interestingly, we show that murine innate cells like IL-2-cultured NK and bone marrow-derived dendritic cells can simultaneously express ICOS and ICOS-Ligand; both molecules are functional in NK intracellular signaling, enhancing early phosphorylation of Akt and Erk, or IFN-γ secretion in IL-2-activated NK cells. Our study shows the functional importance of the ICOS/ICOS-L pair in NK cell homeostasis, differentiation and activity and suggests novel therapeutic targets for NK manipulation.es_ES
dc.description.sponsorshipThis work was supported by grants from the Acción Estratégica en Salud (Instituto de Salud Carlos III, ISCIII, MINECO, Spain) (PI13/02153 and PI16CIII/00012 to P.P.; PI13/01809 to J.M.R.; and PI14/00049 to BdA); grants from Ministerio de Economía y Competitividad MINECO/FEDER, Spain (SAF2015-70880-R to M.L.G. and SAF2014-58052 to D.L.); and grants from Associazione Italiana per la Ricerca sul Cancro, AIRC, Milan (IG20714) and the Fondazione Amici di Jean, Torino, Italy (to U.D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleICOS deficiency hampers the homeostasis, development and function of NK cellses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID31283790es_ES
dc.format.volume14es_ES
dc.format.number7es_ES
dc.format.pagee0219449es_ES
dc.identifier.doi10.1371/journal.pone.0219449es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderItalian Association for Cancer Research 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1932-6203es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0219449es_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI13/02153es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16CIII/00012es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI13/01809es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI14/00049es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-70880-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-58052es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/IG20714es_ES
dc.rights.accessRightsopen accesses_ES


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