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dc.contributor.author | Schetters, Sjoerd T T | |
dc.contributor.author | Kruijssen, Laura J W | |
dc.contributor.author | Crommentuijn, Matheus H W | |
dc.contributor.author | Kalay, Hakan | |
dc.contributor.author | Ochando, Jordi | |
dc.contributor.author | den Haan, Joke M M | |
dc.contributor.author | Garcia-Vallejo, Juan J | |
dc.contributor.author | van Kooyk, Yvette | |
dc.date.accessioned | 2020-01-29T11:41:19Z | |
dc.date.available | 2020-01-29T11:41:19Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Front Immunol. 2018 May 7;9:990. | es_ES |
dc.identifier.issn | 1664-3224 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/8956 | |
dc.description | 339977 | es_ES |
dc.description.abstract | The 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.sponsorship | This work was supported by the European Research Council Advanced grant 339977 to YK, SS, LK, and MC. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Frontiers Media | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | CD209a | es_ES |
dc.subject | SIGNR5 | es_ES |
dc.subject | Antigen delivery | es_ES |
dc.subject | Dendritic cell | es_ES |
dc.subject | Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin | es_ES |
dc.subject | Vaccination | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Animals, Genetically Modified | es_ES |
dc.subject.mesh | Antibodies | es_ES |
dc.subject.mesh | CD4-Positive T-Lymphocytes | es_ES |
dc.subject.mesh | CD8-Positive T-Lymphocytes | es_ES |
dc.subject.mesh | Cell Adhesion Molecules | es_ES |
dc.subject.mesh | Dendritic Cells | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Granulocyte-Macrophage Colony-Stimulating Factor | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Lectins, C-Type | es_ES |
dc.subject.mesh | Macrophages | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Ovalbumin | es_ES |
dc.subject.mesh | Receptors, Cell Surface | es_ES |
dc.subject.mesh | Vaccination | es_ES |
dc.subject.mesh | Adaptive Immunity | es_ES |
dc.subject.mesh | Antigen Presentation | es_ES |
dc.title | Mouse DC-SIGN/CD209a as Target for Antigen Delivery and Adaptive Immunity | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 29867967 | es_ES |
dc.format.volume | 9 | es_ES |
dc.format.page | 990 | es_ES |
dc.identifier.doi | 10.3389/fimmu.2018.00990 | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.3389/fimmu.2018.00990 | es_ES |
dc.identifier.journal | Frontiers in immunology | 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/339977 to YK, SS, LK, and MC | es_ES |
dc.rights.accessRights | open access | es_ES |