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dc.contributor.author | Montes-Casado, Maria | |
dc.contributor.author | Ojeda, Gloria | |
dc.contributor.author | Aragoneses-Fenoll, Laura | |
dc.contributor.author | Lopez, Daniel | |
dc.contributor.author | Andres, Belen de | |
dc.contributor.author | Gaspar, Maria Luisa | |
dc.contributor.author | Dianzani, Umberto | |
dc.contributor.author | Rojo, José M | |
dc.contributor.author | Portoles, Pilar | |
dc.date.accessioned | 2019-11-25T12:58:14Z | |
dc.date.available | 2019-11-25T12:58:14Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | PLoS One. 2019 Jul 8;14(7):e0219449. | es_ES |
dc.identifier.issn | 1932-6203 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/8704 | |
dc.description.abstract | Signaling 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | Public Library of Science (PLOS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | ICOS deficiency hampers the homeostasis, development and function of NK cells | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 31283790 | es_ES |
dc.format.volume | 14 | es_ES |
dc.format.number | 7 | es_ES |
dc.format.page | e0219449 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0219449 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Italian Association for Cancer Research | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1932-6203 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1371/journal.pone.0219449 | es_ES |
dc.identifier.journal | PloS one | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI13/02153 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI16CIII/00012 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI13/01809 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI14/00049 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2015-70880-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2014-58052 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/IG20714 | es_ES |
dc.rights.accessRights | open access | es_ES |