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Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation

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dc.contributor.authorBaroja-Mazo, Alberto
dc.contributor.authorRevilla-Nuin, Beatriz
dc.contributor.authorBejar, Africa de
dc.contributor.authorMartinez-Alarcón, Laura
dc.contributor.authorHerrero, José I.
dc.contributor.authorEl-Tayeb, Ali
dc.contributor.authorMüller, Christa E.
dc.contributor.authorAparicio, Pedro
dc.contributor.authorPons Miñano, José Antonio
dc.contributor.authorPelegrín Vivancos, Pablo
dc.contributor.departmentMedicina
dc.date.accessioned2025-01-26T10:57:05Z
dc.date.available2025-01-26T10:57:05Z
dc.date.issued2018-07-17
dc.description© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons. This document is the Published,version of a Published Work that appeared in final form in American Journal of Transplantation. To access the final edited and published work see https://doi.org/10.1111/ajt.15023
dc.description.abstractThe artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory and effector T cells (Tregs and Teffs, respectively) has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells and, moreover, to examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A2R) in the induction of clinical tolerance after liver transplant. The action of extracellular nucleotides in human T cells was analyzed by in vitro experiments with isolated T cells. Additionally, 17 liver transplant patients were enrolled in an immunosuppression withdrawal trial, and the differences in the CD39‐CD73‐A2R axis were compared between tolerant and nontolerant patients. In contrast to the mice, the activation of human Tregs was inhibited similarly to Teffs in the presence of eADO. Moreover, the expression of the enzyme responsible for the degradation of ADO, adenosine deaminase, was higher in tolerant patients with respect to the nontolerant group along the immunosuppression withdrawal. Our data support the idea that eADO signaling and its degradation may play a role in the complex system of regulation of liver transplant tolerance.es
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dc.format.extent14es
dc.identifier.citationAm J Transplant 2019 19:48–61.
dc.identifier.doihttps://doi.org/10.1111/ajt.15023
dc.identifier.issnPrint: 1600-6135
dc.identifier.issnElectronic: 1600-6143
dc.identifier.urihttp://hdl.handle.net/10201/149315
dc.languageenges
dc.publisherWileyes
dc.relationH2020 European Research Council, Grant/Award Number: ERC-2013-CoG 614578; Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: SAF2017-88276-R; Fundación Mutua Madrileña, Grant/Award Number: FMM13; Instituto de Salud Carlos III, Grant/Award Number: PI12/02042 and PI13/00174es
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1600613522088980?via%3Dihub
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectBasic (laboratory) research/sciencees
dc.subjectCellular biology
dc.subjectImmune regulation
dc.subjectImmunosuppression/immune modulation
dc.subjectImmunosuppressive regimens ‐ minimization/withdrawal
dc.subjectLiver transplantation/hepatology
dc.subjectSIgnaling/signaling pathways
dc.subjectT cell biology
dc.subjectTolerance: Clinical
dc.subjectTranslational research/science
dc.titleExtracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantationes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
relation.isAuthorOfPublication.latestForDiscovery547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
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