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TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity.

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dc.contributor.authorRiquelme, Paloma
dc.contributor.authorHaarer, Jan
dc.contributor.authorKammler, Anja
dc.contributor.authorWalter, Lisa
dc.contributor.authorTomiuk, Stefan
dc.contributor.authorAhrens, Norbert
dc.contributor.authorWege, Anja K
dc.contributor.authorGoecze, Ivan
dc.contributor.authorZecher, Daniel
dc.contributor.authorBanas, Bernhard
dc.contributor.authorSpang, Rainer
dc.contributor.authorFändrich, Fred
dc.contributor.authorLutz, Manfred B
dc.contributor.authorSawitzki, Birgit
dc.contributor.authorSchlitt, Hans J
dc.contributor.authorOchando, Jordi
dc.contributor.authorGeissler, Edward K
dc.contributor.authorHutchinson, James A
dc.contributor.funderUnión Europea. Comisión Europea. 7 Programa Marco
dc.contributor.funderDeutsche Forschungsgemeinschaft (Alemania)
dc.contributor.funderUnión Europea. Comisión Europea. H2020
dc.date.accessioned2020-06-15T06:20:40Z
dc.date.available2020-06-15T06:20:40Z
dc.date.issued2018
dc.description.abstractHuman regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4+ T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4+ T cells to IL-10-producing, TIGIT+ FoxP3+-induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs relies on multiple non-redundant mechanisms that are not exclusive to interaction of Mregs and T cells, including signals mediated by indoleamine 2,3-dioxygenase, TGF-β, retinoic acid, Notch and progestagen-associated endometrial protein. Preoperative administration of donor-derived Mregs to living-donor kidney transplant recipients results in an acute increase in circulating TIGIT+ Tregs. These results suggest a feed-forward mechanism by which Mreg treatment promotes allograft acceptance through rapid induction of direct-pathway Tregs.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThe authors gratefully acknowledge the support of the European Union 7th Framework Programme through The ONE Study initiative (award 260687). This work was also partly funded by the Deutsche Forschungsgemeinschaft (awards HU 1838/1-1 and HU 1838/2-1), the EU-funded Reprogramming the Immune System for Establishment of Tolerance (RISET) network, the Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies (A FACTT) consortium funded by the European Union Horizon 2020 programme and the Regensburg Center for Interventional Immunology. L.W. received an intramural (ReForM-A) award from UKR.es_ES
dc.format.number1es_ES
dc.format.page2858es_ES
dc.format.volume9es_ES
dc.identifier.citationNat Commun . 2018 Jul 20;9(1):2858.es_ES
dc.identifier.doi10.1038/s41467-018-05167-8es_ES
dc.identifier.e-issn2041-1723es_ES
dc.identifier.journalNature communicationses_ES
dc.identifier.pubmedID30030423es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10394
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/award 260687es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/awards HU 1838/1-1es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/HU 1838/2-1es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-018-05167-8es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAllograftses_ES
dc.subject.meshAnimalses_ES
dc.subject.meshCell Differentiationes_ES
dc.subject.meshDendritic Cellses_ES
dc.subject.meshForkhead Transcription Factorses_ES
dc.subject.meshGraft Rejectiones_ES
dc.subject.meshHumanses_ES
dc.subject.meshInterleukin-10es_ES
dc.subject.meshKidney Transplantationes_ES
dc.subject.meshLipopolysaccharide Receptorses_ES
dc.subject.meshMacrophageses_ES
dc.subject.meshMicees_ES
dc.subject.meshPhenotypees_ES
dc.subject.meshReceptors, Immunologices_ES
dc.subject.meshSignal Transductiones_ES
dc.subject.meshT-Lymphocytes, Regulatoryes_ES
dc.subject.meshTransforming Growth Factor betaes_ES
dc.subject.meshTransplantation, Homologouses_ES
dc.titleTIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isAuthorOfPublicationf4411902-c52c-4e77-afff-0f9d9e8d9e9f
relation.isAuthorOfPublication.latestForDiscoveryf4411902-c52c-4e77-afff-0f9d9e8d9e9f
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