Publications
2014
Flacher Vincent, Tripp Christoph H, Mairhofer David G, Steinman Ralph M, Stoitzner Patrizia, Idoyaga Juliana, Romani Nikolaus
Murine Langerin+ dermal dendritic cells prime CD8+ Ŧ cells while Langerhans cells induce cross-tolerance Journal Article
In: EMBO molecular medicine, vol. 6, no. 9, pp. 1191–1204, 2014, ISSN: 1757-4684.
Abstract | Links | BibTeX | Tags: agonists, Animals, Antibodies, antibody, Antigen, Antigen Presentation, Antigens, C-Type, C-type lectin, cancer, CD70, CD8-Positive T-Lymphocytes, CD8+ T cells, CD8+ T‐cell responses, Cellular, CROSS-PRESENTATION, Cross-Priming, Cytotoxicity, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, disease, imiquimod, Immunization, IMMUNOGENICITY, Immunologic Memory, Immunological, Immunology, In vivo, Inbred C57BL, INDUCTION, Intradermal, Langerhans Cells, LECTIN, Lectins, Mannose-Binding Lectins, Maturation, Mice, Models, murine, OVALBUMIN, physiology, priming, RESPONSES, Skin, Surface, T CELLS, T-CELLS, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines
@article{flacher_murine_2014,
title = {Murine Langerin+ dermal dendritic cells prime CD8+ Ŧ cells while Langerhans cells induce cross-tolerance},
author = {Vincent Flacher and Christoph H Tripp and David G Mairhofer and Ralph M Steinman and Patrizia Stoitzner and Juliana Idoyaga and Nikolaus Romani},
doi = {10.15252/emmm.201303283},
issn = {1757-4684},
year = {2014},
date = {2014-09-01},
journal = {EMBO molecular medicine},
volume = {6},
number = {9},
pages = {1191--1204},
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.},
keywords = {agonists, Animals, Antibodies, antibody, Antigen, Antigen Presentation, Antigens, C-Type, C-type lectin, cancer, CD70, CD8-Positive T-Lymphocytes, CD8+ T cells, CD8+ T‐cell responses, Cellular, CROSS-PRESENTATION, Cross-Priming, Cytotoxicity, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, disease, imiquimod, Immunization, IMMUNOGENICITY, Immunologic Memory, Immunological, Immunology, In vivo, Inbred C57BL, INDUCTION, Intradermal, Langerhans Cells, LECTIN, Lectins, Mannose-Binding Lectins, Maturation, Mice, Models, murine, OVALBUMIN, physiology, priming, RESPONSES, Skin, Surface, T CELLS, T-CELLS, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}
2010
Romani Nikolaus, Thurnher Martin, Idoyaga Juliana, Steinman Ralph M, Flacher Vincent
Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy Journal Article
In: Immunology and Cell Biology, vol. 88, no. 4, pp. 424–430, 2010, ISSN: 1440-1711.
Abstract | Links | BibTeX | Tags: Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, C-Type, CD, CD14, CD1a, CROSS-PRESENTATION, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, Immunity, Immunotherapy, INDUCTION, Intradermal, Langerhans Cells, Lectins, Lymphocytes, Mannose-Binding Lectins, mouse, Receptor, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines
@article{romani_targeting_2010,
title = {Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy},
author = {Nikolaus Romani and Martin Thurnher and Juliana Idoyaga and Ralph M Steinman and Vincent Flacher},
doi = {10.1038/icb.2010.39},
issn = {1440-1711},
year = {2010},
date = {2010-01-01},
journal = {Immunology and Cell Biology},
volume = {88},
number = {4},
pages = {424--430},
abstract = {Vaccinations in medicine are commonly administered through the skin. Therefore, the vaccine is immunologically processed by antigen-presenting cells of the skin. There is recent evidence that the clinically less often used intradermal route is effective; in cases even superior to the conventional subcutaneous or intramuscular route. Professional antigen-presenting cells of the skin comprise epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(-) and dermal langerin(+) dendritic cells (DCs). In human skin, langerin(-) dermal DCs can be further subdivided on the basis of their reciprocal CD1a and CD14 expression. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Langerhans cells in human skin seem to be specialized for induction of cytotoxic T lymphocytes. Likewise, mouse Langerhans cells are capable of cross-presentation and of protecting against experimental tumours. It is desirable to harness these properties for immunotherapy. A promising strategy to dramatically improve the outcome of vaccinations is 'antigen targeting'. Thereby, the vaccine is delivered directly and selectively to defined types of skin DCs. Targeting is achieved by means of coupling antigen to antibodies that recognize cell surface receptors on DCs. This approach is being widely explored. Little is known, however, about the events that take place in the skin and the DCs subsets involved therein. This topic will be discussed in this article.},
keywords = {Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, C-Type, CD, CD14, CD1a, CROSS-PRESENTATION, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, Immunity, Immunotherapy, INDUCTION, Intradermal, Langerhans Cells, Lectins, Lymphocytes, Mannose-Binding Lectins, mouse, Receptor, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}