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dc.contributor.authorSchetters, Sjoerd T T
dc.contributor.authorKruijssen, Laura J W
dc.contributor.authorCrommentuijn, Matheus H W
dc.contributor.authorKalay, Hakan
dc.contributor.authorOchando, Jordi 
dc.contributor.authorden Haan, Joke M M
dc.contributor.authorGarcia-Vallejo, Juan J
dc.contributor.authorvan Kooyk, Yvette
dc.date.accessioned2020-01-29T11:41:19Z
dc.date.available2020-01-29T11:41:19Z
dc.date.issued2018
dc.identifier.citationFront Immunol. 2018 May 7;9:990.es_ES
dc.identifier.issn1664-3224es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8956
dc.description339977es_ES
dc.description.abstractThe efficacy of vaccination studies aimed at targeting antigens to human DC-SIGN (hDC-SIGN) have been notoriously difficult to study in vivo, as eight dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) homologs have been described in mice. CD209a/SIGNR5 has been coined as the mouse DC-SIGN (mDC-SIGN) ortholog, based on its expression and location in the genome. Nonetheless, which properties of hDC-SIGN are covered by mDC-SIGN is poorly investigated. One of the most important functions of DC-SIGN is the induction of adaptive immunity. As such, the aim of this study is to determine the capability of mDC-SIGN to induce adaptive immune responses. Here, we show that mDC-SIGN is expressed on GM-CSF cultured bone marrow-derived dendritic cells (BMDCs) and macrophages. However, mDC-SIGN is an internalizing receptor which, unlike hDC-SIGN, quickly resurfaces after internalization. Binding of OVA-coupled anti-mDC-SIGN antibody by BMDCs leads to quick internalization, processing, and presentation to antigen-specific CD8+ and CD4+ T cells, which can be boosted using the TLR4 ligand, monophosphoryl lipid A. In the homeostatic condition, mDC-SIGN is mostly expressed on myeloid cells in the skin and spleen. A subcutaneous injection of fluorescent anti-mDC-SIGN reveals specific targeting to mDC-SIGN+ skin dendritic cells (DCs) and monocyte-derived DCs in situ. A subcutaneous vaccination strategy containing OVA-coupled anti-mDC-SIGN antibody generated antigen-specific polyfunctional CD8+ T cell and CD4+ T cell responses and a strong isotype-switched OVA-specific antibody response in vivo. We conclude that mDC-SIGN shows partly overlapping similarities to hDC-SIGN and that targeting mDC-SIGN provides a valuable approach to investigate the immunological function of DC-SIGN in vivo.es_ES
dc.description.sponsorshipThis work was supported by the European Research Council Advanced grant 339977 to YK, SS, LK, and MC.es_ES
dc.language.isoenges_ES
dc.publisherFrontiers Media es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCD209aes_ES
dc.subjectSIGNR5es_ES
dc.subjectAntigen deliveryes_ES
dc.subjectDendritic celles_ES
dc.subjectDendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrines_ES
dc.subjectVaccinationes_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAnimals, Genetically Modified es_ES
dc.subject.meshAntibodies es_ES
dc.subject.meshCD4-Positive T-Lymphocytes es_ES
dc.subject.meshCD8-Positive T-Lymphocytes es_ES
dc.subject.meshCell Adhesion Molecules es_ES
dc.subject.meshDendritic Cells es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLectins, C-Type es_ES
dc.subject.meshMacrophages es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshOvalbumin es_ES
dc.subject.meshReceptors, Cell Surface es_ES
dc.subject.meshVaccination es_ES
dc.subject.meshAdaptive Immunity es_ES
dc.subject.meshAntigen Presentation es_ES
dc.titleMouse DC-SIGN/CD209a as Target for Antigen Delivery and Adaptive Immunityes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29867967es_ES
dc.format.volume9es_ES
dc.format.page990es_ES
dc.identifier.doi10.3389/fimmu.2018.00990es_ES
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.3389/fimmu.2018.00990es_ES
dc.identifier.journalFrontiers in immunologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/339977 to YK, SS, LK, and MCes_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
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