title: Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross-tolerance.
abstract: Skin 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.
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria Oncotyrol Center for Personalized Cancer Medicine, Innsbruck, Austria.
authors.forename: Vincent
authors.initials: V
authors.lastname: Flacher
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria Oncotyrol Center for Personalized Cancer Medicine, Innsbruck, Austria.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Tripp
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: David G
authors.initials: DG
authors.lastname: Mairhofer
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY, USA.
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria nikolaus.romani@i-med.ac.at patrizia.stoitzner@i-med.ac.at.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY, USA.
authors.forename: Juliana
authors.initials: J
authors.lastname: Idoyaga
authors.affiliation: Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria Oncotyrol Center for Personalized Cancer Medicine, Innsbruck, Austria nikolaus.romani@i-med.ac.at patrizia.stoitzner@i-med.ac.at.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Romani
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D007156:Immunologic Memory; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D037241:Mannose-Binding Lectins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological
chemical_list: D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins
keywords: CD8+ T‐cell responses; Langerhans cells; dendritic cells; skin; tolerance
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