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dc.contributor.authorHerrero Sánchez, María del Carmen 
dc.contributor.authorRodríguez Serrano, Concepción
dc.contributor.authorAlmeida Parra, Julia
dc.contributor.authorSan Segundo Payo, Laura
dc.contributor.authorInogés Sancho, Laura
dc.contributor.authorSantos-Briz Terrón, Ángel
dc.contributor.authorGarcía Briñón, Jesús
dc.contributor.authorSan Miguel Izquierdo, Jesús F.
dc.contributor.authorCañizo Fernández-Roldán, Consuelo del
dc.contributor.authorBlanco Durango, Belén
dc.date.accessioned2022-09-16T12:35:58Z
dc.date.available2022-09-16T12:35:58Z
dc.date.issued2016
dc.identifier.citationBritish Journal of Haematology (BJHaem), 2016, Vol. 173, Nº. 5, págs. 754–768es
dc.identifier.issn0007-1048es
dc.identifier.urihttps://uvadoc.uva.es/handle/10324/55160
dc.descriptionProducción Científicaes
dc.description.abstractThe mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function of T cells, which play an essential role in the development of graft-versus-host disease (GvHD). Despite its partial ability to block mTOR pathway, the mTORC1 inhibitor rapamycin has shown encouraging results in the control of GvHD. Therefore, we considered that simultaneous targeting of both mTORC1 and mTORC2 complexes could exert a more potent inhibition of T cell activation and, thus, could have utility in GvHD control. To assess this assumption, we have used the dual mTORC1/mTORC2 inhibitors CC214-1 and CC214-2. In vitro studies confirmed the superior ability of CC214-1 versus rapamycin to block mTORC1 and mTORC2 activity and to reduce T cell proliferation. Both drugs induced a similar decrease in Th1/Th2 cytokine secretion, but CC214-1 was more efficient in inhibiting na€ıve T cell activation and the expression of Tcell activation markers. In addition, CC214-1 induced specific tolerance against alloantigens, while preserving anti-cytomegalovirus response. Finally, in a mouse model of GvHD, the administration of CC214-2 significantly improved mice survival and decreased GvHD-induced damages. In conclusion, the current study shows, for the first time, the immunosuppressive ability of CC214-1 on T lymphocytes and illustrates the role of CC214-2 in the allogeneic transplantation setting as a possible GvHD prophylaxis agent.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherJohn Wiley & Sonses
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectGraft versus host diseasees
dc.subjectCell transplantationes
dc.subjectTrasplante de célulases
dc.subjectPharmacologyes
dc.subject.classificationMTOR inhibitorses
dc.titleEffect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease controles
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© John Wiley & Sonses
dc.identifier.doi10.1111/bjh.13984es
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/10.1111/bjh.13984es
dc.identifier.publicationfirstpage754es
dc.identifier.publicationissue5es
dc.identifier.publicationlastpage768es
dc.identifier.publicationtitleBritish Journal of Haematologyes
dc.identifier.publicationvolume173es
dc.peerreviewedSIes
dc.description.projectGerencia Regional de Salud de Castilla y León (Proyecto GRS 726/A13)es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones
dc.subject.unesco3205.04 Hematologíaes
dc.subject.unesco3201.01 Oncologíaes


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