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dc.contributor.authorBraza, Mounia S
dc.contributor.authorvan Leent, Mandy M T
dc.contributor.authorLameijer, Marnix
dc.contributor.authorSanchez-Gaytan, Brenda L
dc.contributor.authorArts, Rob J W
dc.contributor.authorPerez-Medina, Carlos 
dc.contributor.authorGonzalez-Perez, Maria 
dc.contributor.authorBrahmachary, Manisha
dc.contributor.authorFay, Francois
dc.contributor.authorKluza, Ewelina
dc.contributor.authorKossatz, Susanne
dc.contributor.authorDress, Regine J
dc.contributor.authorSalem, Fadi
dc.contributor.authorRialdi, Alexander
dc.contributor.authorReiner, Thomas
dc.contributor.authorBoros, Peter
dc.contributor.authorStrijkers, Gustav J
dc.contributor.authorCalcagno, Claudia C
dc.contributor.authorGinhoux, Florent
dc.contributor.authorMarazzi, Ivan
dc.contributor.authorLutgens, Esther
dc.contributor.authorNicolaes, Gerry A F
dc.contributor.authorWeber, Christian
dc.contributor.authorSwirski, Filip K
dc.contributor.authorNahrendorf, Matthias
dc.contributor.authorFisher, Edward A
dc.contributor.authorDuivenvoorden, Raphaël
dc.contributor.authorFayad, Zahi A
dc.contributor.authorNetea, Mihai G
dc.contributor.authorMulder, Willem J M
dc.contributor.authorOchando, Jordi 
dc.contributor.authorConde-San Román, Patricia 
dc.contributor.authorRodriguez-Garcia, Mercedes 
dc.date.accessioned2020-06-15T06:19:11Z
dc.date.available2020-06-15T06:19:11Z
dc.date.issued2018
dc.identifier.citationImmunity . 2018 Nov 20;49(5):819-828.e6.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10393
dc.description.abstractInducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Using an experimental transplantation mouse model, we demonstrate that local macrophage activation through dectin-1 and toll-like receptor 4 (TLR4) drives trained immunity-associated cytokine production during allograft rejection. We conducted nanoimmunotherapeutic studies and found that a short-term mTOR-specific high-density lipoprotein (HDL) nanobiologic treatment (mTORi-HDL) averted macrophage aerobic glycolysis and the epigenetic modifications underlying inflammatory cytokine production. The resulting regulatory macrophages prevented alloreactive CD8+ T cell-mediated immunity and promoted tolerogenic CD4+ regulatory T (Treg) cell expansion. To enhance therapeutic efficacy, we complemented the mTORi-HDL treatment with a CD40-TRAF6-specific nanobiologic (TRAF6i-HDL) that inhibits co-stimulation. This synergistic nanoimmunotherapy resulted in indefinite allograft survival. Together, we show that HDL-based nanoimmunotherapy can be employed to control macrophage function in vivo. Our strategy, focused on preventing inflammatory innate immune responses, provides a framework for developing targeted therapies that promote immunological tolerance.es_ES
dc.description.sponsorshipFunding for this research was provided by: National Institutes of Health (R01 EB009638, R01 HL144072, P01 HL131478, EB009638, R01 HL118440, R01 HL125703, R01 AI139623) Netherlands Organisation for Scientific Research (ZonMW Veni 016156059, ZonMW Vidi 91713324, ZonMW Vici 91818622) Comunidad de Madrid (B2017/BMD-3731) American Heart Association (16SDG27250090) NIH Program of Excellence in Nanotechnology (HHSN368201000045C, K25 EB016673, P30 CA008748) Harold S. Geneen Charitable Trust Spanish Ministry of Science (SAF2016-80031-R) ERC Consolidator (310372)es_ES
dc.language.isoenges_ES
dc.publisherElsevier es_ES
dc.type.hasVersionAMes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshImmunosuppression es_ES
dc.subject.meshOrgan Transplantation es_ES
dc.subject.meshAllografts es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBiomarkers es_ES
dc.subject.meshGraft Survival es_ES
dc.subject.meshHMGB1 Protein es_ES
dc.subject.meshImmune Tolerance es_ES
dc.subject.meshImmunity, Innate es_ES
dc.subject.meshImmunologic Memory es_ES
dc.subject.meshInflammation es_ES
dc.subject.meshMacrophages es_ES
dc.subject.meshMice es_ES
dc.subject.meshMyeloid Cells es_ES
dc.subject.meshTOR Serine-Threonine Kinases es_ES
dc.subject.meshVimentin es_ES
dc.titleInhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID30413362es_ES
dc.format.volume49es_ES
dc.format.number5es_ES
dc.format.page819-828.e6es_ES
dc.identifier.doi10.1016/j.immuni.2018.09.008es_ES
dc.contributor.funderNational Institutes of Health (Estados Unidos) 
dc.contributor.funderDutch Research Council (Holanda) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderAmerican Heart Association 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1097-4180es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.immuni.2018.09.008es_ES
dc.identifier.journalImmunityes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/R01 EB009638es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/R01 HL144072es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ P01 HL131478es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/EB009638es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/R01 HL118440es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/R01 HL125703es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/R01 AI139623es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ZonMW Veni 016156059es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ZonMW Vidi 91713324es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ZonMW Vici 91818622es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/B2017/BMD-3731es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/16SDG27250090es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/HHSN368201000045Ces_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/K25 EB016673es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/P30 CA008748es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2016-80031-Res_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/310372es_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional