title: In situ Delivery of Antigen to DC-SIGN(+)CD14(+) Dermal Dendritic Cells Results in Enhanced CD8(+) T-Cell Responses.
abstract: CD14(+) dendritic cells (DCs) present in the dermis of human skin represent a large subset of dermal DCs (dDCs) that are considered macrophage-like cells with poor antigen (cross)-presenting capacity and limited migratory potential to the lymph nodes. CD14(+) dDC highly express DC-specific ICAM-3-grabbing non-integrin (DC-SIGN), a receptor containing potent endocytic capacity, facilitating intracellular routing of antigens to major histocompatibility complex I and II (MHC-I andII) loading compartments for the presentation to antigen-specific CD8(+) and CD4(+) T cells. Here we show using a human skin explant model that the in situ targeting of antigens to DC-SIGN using glycan-modified liposomes enhances the antigen-presenting capacity of CD14(+) dDCs. Intradermal vaccination of liposomes modified with the DC-SIGN-targeting glycan Lewis(X), containing melanoma antigens (MART-1 or Gp100), accumulated in CD14(+) dDCs and resulted in enhanced Gp100- or MART-1-specific CD8(+) T-cell responses. Simultaneous intradermal injection of the cytokines GM-CSF and IL-4 as adjuvant enhanced the migration of the skin DCs and increased the expression of DC-SIGN on the CD14(+) and CD1a(+) dDCs. These data demonstrate that human CD14(+) dDCs exhibit potent cross-presenting capacity when targeted in situ through DC-SIGN.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Fehres
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands.
authors.forename: Astrid J
authors.initials: AJ
authors.lastname: van Beelen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands.
authors.forename: Sven C M
authors.initials: SCM
authors.lastname: Bruijns
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands.
authors.forename: Martino
authors.initials: M
authors.lastname: Ambrosini
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kalay
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
authors.forename: Louis van
authors.initials: LV
authors.lastname: Bloois
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands.
authors.forename: Wendy W J
authors.initials: WWJ
authors.lastname: Unger
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Garcia-Vallejo
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands; MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Medical Oncology, VUmc Amsterdam, The Netherlands.
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc Amsterdam, The Netherlands. Electronic address: y.vankooyk@vumc.nl.
authors.forename: Yvette van
authors.initials: YV
authors.lastname: Kooyk
mesh_terms: D000704:Analysis of Variance; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology* / Q000378:metabolism; D008081:Liposomes / Q000276:immunology / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology*; D012494:Sampling Studies; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin