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 Article de journal
Dans: EMBO molecular medicine, vol. 6, no. 9, p. 1191–1204, 2014, ISSN: 1757-4684.
Résumé | Liens | BibTeX | Étiquettes: 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}
}
Flacher V, Tripp C H, Haid B, Kissenpfennig A, Malissen B, Stoitzner P, Idoyaga J, Romani N
Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ Ŧ cell responses Article de journal
Dans: Journal of Immunology, vol. 188, no. 1550-6606 (Electronic), p. 2146–2155, 2012.
Résumé | BibTeX | Étiquettes: administration & dosage, Animals, Antibodies, antibody, Antigen, Antigens, Biosynthesis, C-Type, C-type lectin, CD, Cell Surface, Comparative Study, Cytotoxic, Dendritic Cells, DERMATOLOGY, Gene Knock-In Techniques, Genetics, imiquimod, immune response, IMMUNE-RESPONSES, Immunization, Immunology, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, inflammation, Inflammation Mediators, Injections, Intradermal, knock-in, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, mAb, Mannose-Binding Lectins, MEDIATOR, metabolism, Mice, Minor Histocompatibility Antigens, mouse, murine, Organ Culture Techniques, Ovum, pathology, physiology, Protein, Protein Transport, Rats, Receptor, Receptors, RESPONSES, Skin, SUBSETS, Surface, T-Lymphocytes, target, Team-Mueller, TLR7, transgenic
@article{flacher_skin_2012,
title = {Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ Ŧ cell responses},
author = {V Flacher and C H Tripp and B Haid and A Kissenpfennig and B Malissen and P Stoitzner and J Idoyaga and N Romani},
year = {2012},
date = {2012-03-01},
journal = {Journal of Immunology},
volume = {188},
number = {1550-6606 (Electronic)},
pages = {2146--2155},
abstract = {Incorporation of Ags by dendritic cells (DCs) increases when Ags are targeted to endocytic receptors by mAbs. We have previously demonstrated in the mouse that mAbs against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerin(neg) DCs, and dermal Langerin(+) DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after Ag targeting has not been addressed in vivo. We show in this study that murine epidermal LCs and dermal DCs transport intradermally injected mAbs against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAbs migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAbs were found in resident CD8alpha(+) DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin(+) DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where OVA-coupled anti-DEC-205 had been injected decreased endogenous cytotoxic responses against OVA peptide-loaded target cells by 40-50%. Surprisingly, selective ablation of all Langerin(+) skin DCs in Langerin-DTR knock-in mice did not affect such responses independently of the adjuvant chosen. Thus, in cutaneous immunization strategies where Ag is targeted to DCs, Langerin(+) skin DCs play a major role in transport of anti-DEC-205 mAb, although Langerin(neg) dermal DCs and CD8alpha(+) DCs are sufficient to subsequent CD8(+) T cell responses},
keywords = {administration & dosage, Animals, Antibodies, antibody, Antigen, Antigens, Biosynthesis, C-Type, C-type lectin, CD, Cell Surface, Comparative Study, Cytotoxic, Dendritic Cells, DERMATOLOGY, Gene Knock-In Techniques, Genetics, imiquimod, immune response, IMMUNE-RESPONSES, Immunization, Immunology, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, inflammation, Inflammation Mediators, Injections, Intradermal, knock-in, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, mAb, Mannose-Binding Lectins, MEDIATOR, metabolism, Mice, Minor Histocompatibility Antigens, mouse, murine, Organ Culture Techniques, Ovum, pathology, physiology, Protein, Protein Transport, Rats, Receptor, Receptors, RESPONSES, Skin, SUBSETS, Surface, T-Lymphocytes, target, Team-Mueller, TLR7, transgenic},
pubstate = {published},
tppubtype = {article}
}
Canard B, Vachon H, Fontaine T, Pin J J, Paul S, Genin C, Mueller C G
Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue Article de journal
Dans: Immunol.Lett., vol. 135, no. 1879-0542 (Electronic), p. 165–172, 2011.
Résumé | BibTeX | Étiquettes: Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus
@article{canard_generation_2011,
title = {Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue},
author = {B Canard and H Vachon and T Fontaine and J J Pin and S Paul and C Genin and C G Mueller},
year = {2011},
date = {2011-01-01},
journal = {Immunol.Lett.},
volume = {135},
number = {1879-0542 (Electronic)},
pages = {165--172},
abstract = {DC-SIGN is a C-type lectin of recognized importance in immunology and in the pathogenicity human pathogens. Monoclonal antibodies directed against DC-SIGN have been generated, but their systemic characterization for interfering with binding of the HIV-1 glycoprotein 120 has often been omitted. Moreover, so far, no anti-DC-SIGN monoclonal antibody has been described that recognizes its antigen after formalin fixation and paraffin embedding. In this study, we have generated new anti-DC-SIGN monoclonal antibodies using HeLa cells stably expressing DC-SIGN as immunogen. We have obtained 11 hybridoma clones producing antibodies that recognized DC-SIGN on monocyte-derived dendritic cells and on dermal-type macrophages. Seven monoclonal antibodies displayed a capacity to interfere with DC-SIGN binding to HIV-1 gp120. One recognized DC-SIGN on formalin-fixed dendritic cells and macrophages. Using this antibody we have obtained specific labelling of DC-SIGN and colocalisation with the dermal macrophage marker CD163 on human skin. The described monoclonal anti-human DC-SIGN antibodies will be of use to the scientific community to address fundamental immunology issues, in particular concerning macrophages and dendritic cells, and help elucidate infection events of pathogen targeting DC-SIGN as recognition receptor},
keywords = {Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus},
pubstate = {published},
tppubtype = {article}
}
Flacher Vincent, Tripp Christoph H, Stoitzner Patrizia, Haid Bernhard, Ebner Susanne, Frari Barbara Del, Koch Franz, Park Chae Gyu, Steinman Ralph M, Idoyaga Juliana, Romani Nikolaus
Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis Article de journal
Dans: The Journal of Investigative Dermatology, vol. 130, no. 3, p. 755–762, 2010, ISSN: 1523-1747.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibodies, antibody, Antigen, Antigen Presentation, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, BASEMENT MEMBRANE, C-Type, C-type lectin, CD103, CD8+ T cells, Cell Division, Cell Movement, Cells, Culture, Cultured, cytology, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermal Cells, Epidermis, function, Human, Humans, Immunology, in situ, IN VITRO, In vivo, Inbred BALB C, Inbred C57BL, Injections, Intradermal, Langerhans Cells, LECTIN, Lectins, mAb, Mannose-Binding Lectins, Membrane, Mice, Monoclonal, mouse, murine, Pharmacology, Proliferation, Protein, Receptor, Skin, Surface, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Vaccination, vaccine, Vaccines
@article{flacher_epidermal_2010,
title = {Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis},
author = {Vincent Flacher and Christoph H Tripp and Patrizia Stoitzner and Bernhard Haid and Susanne Ebner and Barbara Del Frari and Franz Koch and Chae Gyu Park and Ralph M Steinman and Juliana Idoyaga and Nikolaus Romani},
doi = {10.1038/jid.2009.343},
issn = {1523-1747},
year = {2010},
date = {2010-03-01},
journal = {The Journal of Investigative Dermatology},
volume = {130},
number = {3},
pages = {755--762},
abstract = {Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.},
keywords = {Animals, Antibodies, antibody, Antigen, Antigen Presentation, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, BASEMENT MEMBRANE, C-Type, C-type lectin, CD103, CD8+ T cells, Cell Division, Cell Movement, Cells, Culture, Cultured, cytology, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermal Cells, Epidermis, function, Human, Humans, Immunology, in situ, IN VITRO, In vivo, Inbred BALB C, Inbred C57BL, Injections, Intradermal, Langerhans Cells, LECTIN, Lectins, mAb, Mannose-Binding Lectins, Membrane, Mice, Monoclonal, mouse, murine, Pharmacology, Proliferation, Protein, Receptor, Skin, Surface, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Vaccination, vaccine, Vaccines},
pubstate = {published},
tppubtype = {article}
}