Schetters, Sjoerd T TKruijssen, Laura J WCrommentuijn, Matheus H WKalay, HakanOchando, Jordiden Haan, Joke M MGarcia-Vallejo, Juan Jvan Kooyk, Yvette2020-01-292020-01-292018Front Immunol. 2018 May 7;9:990.1664-3224http://hdl.handle.net/20.500.12105/8956339977The 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.engVoRhttp://creativecommons.org/licenses/by/4.0/CD209aSIGNR5Antigen deliveryDendritic cellDendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrinVaccinationAnimalsAnimals, Genetically ModifiedAntibodiesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Adhesion MoleculesDendritic CellsFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansLectins, C-TypeMacrophagesMaleMiceMice, Inbred C57BLOvalbuminReceptors, Cell SurfaceVaccinationAdaptive ImmunityAntigen PresentationAtribución 4.0 Internacional29867967999010.3389/fimmu.2018.00990Frontiers in immunologyopen access