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- Title
In situ Delivery of Antigen to DC-SIGN<sup>+</sup>CD14<sup>+</sup> Dermal Dendritic Cells Results in Enhanced CD8<sup>+</sup> T-Cell Responses.
- Authors
Fehres, Cynthia M; van Beelen, Astrid J; Bruijns, Sven C M; Ambrosini, Martino; Kalay, Hakan; Bloois, Louis van; Unger, Wendy W J; Garcia-Vallejo, Juan J; Storm, Gert; de Gruijl, Tanja D; Kooyk, Yvette van
- 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 LewisX, 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.
- Subjects
DENDRITIC cells; MACROPHAGES; T cells; INTRADERMAL injections; LIPOSOMES
- Publication
Journal of Investigative Dermatology, 2015, Vol 135, Issue 9, p2228
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2015.152