2026-04-26T23:28:58Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/87042024-09-27T22:01:24Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud author Montes-Casado, Maria author Ojeda, Gloria author Aragoneses-Fenoll, Laura author Lopez, Daniel author Andres, Belen de author Gaspar, Maria Luisa author Dianzani, Umberto author Rojo, José M author Portoles, Pilar funder Instituto de Salud Carlos III funder Ministerio de Economía y Competitividad (España) funder Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) funder Italian Association for Cancer Research 2019-11-25T12:58:14Z 2019-11-25T12:58:14Z 2019 PLoS One. 2019 Jul 8;14(7):e0219449. 1932-6203 http://hdl.handle.net/20.500.12105/8704 31283790 10.1371/journal.pone.0219449 1932-6203 PloS one 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. eng ICOS deficiency hampers the homeostasis, development and function of NK cells journal article 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 URL https://repisalud.isciii.es/bitstreams/63080a58-fb1a-48d3-805e-4a92d4146e07/download File MD5 38d831cb601ccfda00b5913b6ce33915 3586736 application/pdf ICOSDeficiencyHampersThe_2019.pdf URL https://repisalud.isciii.es/bitstreams/19e6ffaa-4b89-4ad8-96b3-674d0a4b6579/download File MD5 facd1f57097fdfcbbd7562ecdf9f68e0 85380 text/plain ICOSDeficiencyHampersThe_2019.pdf.txt