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dc.contributor.author | Braza, Mounia S | |
dc.contributor.author | van Leent, Mandy M T | |
dc.contributor.author | Lameijer, Marnix | |
dc.contributor.author | Sanchez-Gaytan, Brenda L | |
dc.contributor.author | Arts, Rob J W | |
dc.contributor.author | Perez-Medina, Carlos | |
dc.contributor.author | Gonzalez-Perez, Maria | |
dc.contributor.author | Brahmachary, Manisha | |
dc.contributor.author | Fay, Francois | |
dc.contributor.author | Kluza, Ewelina | |
dc.contributor.author | Kossatz, Susanne | |
dc.contributor.author | Dress, Regine J | |
dc.contributor.author | Salem, Fadi | |
dc.contributor.author | Rialdi, Alexander | |
dc.contributor.author | Reiner, Thomas | |
dc.contributor.author | Boros, Peter | |
dc.contributor.author | Strijkers, Gustav J | |
dc.contributor.author | Calcagno, Claudia C | |
dc.contributor.author | Ginhoux, Florent | |
dc.contributor.author | Marazzi, Ivan | |
dc.contributor.author | Lutgens, Esther | |
dc.contributor.author | Nicolaes, Gerry A F | |
dc.contributor.author | Weber, Christian | |
dc.contributor.author | Swirski, Filip K | |
dc.contributor.author | Nahrendorf, Matthias | |
dc.contributor.author | Fisher, Edward A | |
dc.contributor.author | Duivenvoorden, Raphaël | |
dc.contributor.author | Fayad, Zahi A | |
dc.contributor.author | Netea, Mihai G | |
dc.contributor.author | Mulder, Willem J M | |
dc.contributor.author | Ochando, Jordi | |
dc.contributor.author | Conde-San Román, Patricia | |
dc.contributor.author | Rodriguez-Garcia, Mercedes | |
dc.date.accessioned | 2020-06-15T06:19:11Z | |
dc.date.available | 2020-06-15T06:19:11Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Immunity . 2018 Nov 20;49(5):819-828.e6. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/10393 | |
dc.description.abstract | Inducing 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.sponsorship | Funding 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.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Immunosuppression | es_ES |
dc.subject.mesh | Organ Transplantation | es_ES |
dc.subject.mesh | Allografts | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Biomarkers | es_ES |
dc.subject.mesh | Graft Survival | es_ES |
dc.subject.mesh | HMGB1 Protein | es_ES |
dc.subject.mesh | Immune Tolerance | es_ES |
dc.subject.mesh | Immunity, Innate | es_ES |
dc.subject.mesh | Immunologic Memory | es_ES |
dc.subject.mesh | Inflammation | es_ES |
dc.subject.mesh | Macrophages | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Myeloid Cells | es_ES |
dc.subject.mesh | TOR Serine-Threonine Kinases | es_ES |
dc.subject.mesh | Vimentin | es_ES |
dc.title | Inhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 30413362 | es_ES |
dc.format.volume | 49 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | 819-828.e6 | es_ES |
dc.identifier.doi | 10.1016/j.immuni.2018.09.008 | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | |
dc.contributor.funder | Dutch Research Council (Holanda) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | American Heart Association | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1097-4180 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.immuni.2018.09.008 | es_ES |
dc.identifier.journal | Immunity | 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/R01 EB009638 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/R01 HL144072 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/ P01 HL131478 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/EB009638 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/R01 HL118440 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/R01 HL125703 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/R01 AI139623 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/ZonMW Veni 016156059 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/ZonMW Vidi 91713324 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/ZonMW Vici 91818622 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/B2017/BMD-3731 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/16SDG27250090 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/HHSN368201000045C | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/K25 EB016673 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/P30 CA008748 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2016-80031-R | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/310372 | es_ES |
dc.rights.accessRights | open access | es_ES |