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Medientyp:
E-Artikel
Titel:
Murine Langerin+ dermal dendritic cells prime CD8+T cells while Langerhans cells induce cross‐tolerance
Beteiligte:
Flacher, Vincent;
Tripp, Christoph H;
Mairhofer, David G;
Steinman, Ralph M;
Stoitzner, Patrizia;
Idoyaga, Juliana;
Romani, Nikolaus
Erschienen:
Springer Science and Business Media LLC, 2014
Erschienen in:
EMBO Molecular Medicine, 6 (2014) 9, Seite 1191-1204
Sprache:
Englisch
DOI:
10.15252/emmm.201303283
ISSN:
1757-4676;
1757-4684
Entstehung:
Anmerkungen:
Beschreibung:
AbstractSkin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C‐type lectin Langerin/CD207 are cross‐presented to CD8+ T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti‐CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)‐coupled anti‐Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin+ dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8+ T‐cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross‐presentation to CD8+ T cells. Langerin/OVA combined with imiquimod could not prime CD8+ T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin+ dDCs prime long‐lasting cytotoxic responses, while cross‐presentation by LCs negatively influences CD8+ T‐cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.