Jacquemin Clément, Schmitt Nathalie, Contin-Bordes Cécile, Liu Yang, Narayanan Priya, Seneschal Julien, Maurouard Typhanie, Dougall David, Davizon Emily Spence, Dumortier Hélène, Douchet Isabelle, Raffray Loïc, Richez Christophe, Lazaro Estibaliz, Duffau Pierre, Truchetet Marie-Elise, Khoryati Liliane, Mercié Patrick, Couzi Lionel, Merville Pierre, Schaeverbeke Thierry, Viallard Jean-François, Pellegrin Jean-Luc, Moreau Jean-François, Muller Sylviane, Zurawski Sandy, Coffman Robert L, Pascual Virginia, Ueno Hideki, Blanco Patrick
OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response Journal Article
In: Immunity, vol. 42, no. 6, pp. 1159–1170, 2015, ISSN: 1097-4180.
Abstract | Links | BibTeX | Tags: Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult
@article{jacquemin_ox40_2015,
title = {OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response},
author = {Clément Jacquemin and Nathalie Schmitt and Cécile Contin-Bordes and Yang Liu and Priya Narayanan and Julien Seneschal and Typhanie Maurouard and David Dougall and Emily Spence Davizon and Hélène Dumortier and Isabelle Douchet and Loïc Raffray and Christophe Richez and Estibaliz Lazaro and Pierre Duffau and Marie-Elise Truchetet and Liliane Khoryati and Patrick Mercié and Lionel Couzi and Pierre Merville and Thierry Schaeverbeke and Jean-François Viallard and Jean-Luc Pellegrin and Jean-François Moreau and Sylviane Muller and Sandy Zurawski and Robert L Coffman and Virginia Pascual and Hideki Ueno and Patrick Blanco},
doi = {10.1016/j.immuni.2015.05.012},
issn = {1097-4180},
year = {2015},
date = {2015-01-01},
journal = {Immunity},
volume = {42},
number = {6},
pages = {1159--1170},
abstract = {Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.},
keywords = {Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult},
pubstate = {published},
tppubtype = {article}
}
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}
}
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 Journal Article
In: The Journal of Investigative Dermatology, vol. 130, no. 3, pp. 755–762, 2010, ISSN: 1523-1747.
Abstract | Links | BibTeX | Tags: 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}
}
Dumortier Hélène, van Mierlo Geertje J D, Egan Deirdre, van Ewijk Willem, Toes René E M, Offringa Rienk, Melief Cornelis J M
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 175, no. 2, pp. 855–863, 2005, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: Adenovirus E1A Proteins, Animals, Antigen, Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Cell Movement, Clonal Deletion, Cytotoxic, Cytotoxicity, Dendritic Cells, Down-Regulation, Dumortier, Epitopes, Female, I2CT, Immunologic, Immunologic Memory, Inbred C57BL, Lipopolysaccharides, Lymphocyte Activation, Mice, Myeloid Cells, Receptors, Regulatory, T-Cell, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic
@article{dumortier_antigen_2005,
title = {Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like Ŧ cells that can be rescued for full effector function},
author = {Hélène Dumortier and Geertje J D van Mierlo and Deirdre Egan and Willem van Ewijk and René E M Toes and Rienk Offringa and Cornelis J M Melief},
doi = {10.4049/jimmunol.175.2.855},
issn = {0022-1767},
year = {2005},
date = {2005-01-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {175},
number = {2},
pages = {855--863},
abstract = {Immature dendritic cells (DC), in contrast to their mature counterparts, are incapable of mobilizing a CD8+ CTL response, and, instead, have been reported to induce CTL tolerance. We directly addressed the impact of immature vs mature DC on CTL responses by infusing adenovirus peptide-loaded DC (of the D1 cell line) into mice that had received adenovirus-specific naive TCR-transgenic CD8+ T cells. Whereas i.v. injection of mature DC triggered vigorous CTL expansion, immature DC elicited little proliferation involving only a minority of the TCR-transgenic CTL. Even though the latter CTL developed effector functions, including cytolytic activity and proinflammatory cytokine secretion, these cells differed significantly from CTL primed by mature DC in that they did not exhibit down-regulation of CD62L and CCR7, receptors involved in trapping of T cells in the lymphoid organs. Interestingly, adoptive transfer of CTL effector cells harvested after priming by either mature or immature DC into naive recipient mice, followed by exposure to adenovirus, yielded quantitatively and qualitatively indistinguishable CTL memory responses. Therefore, in vivo priming of naive CD8+ T cells by immature DC, although failing to induce a full-blown, systemic CTL response, resulted in the formation of central memory-like T cells that were able to expand and produce IFN-gamma upon secondary antigenic stimulation.},
keywords = {Adenovirus E1A Proteins, Animals, Antigen, Antigen Presentation, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Cell Movement, Clonal Deletion, Cytotoxic, Cytotoxicity, Dendritic Cells, Down-Regulation, Dumortier, Epitopes, Female, I2CT, Immunologic, Immunologic Memory, Inbred C57BL, Lipopolysaccharides, Lymphocyte Activation, Mice, Myeloid Cells, Receptors, Regulatory, T-Cell, T-Lymphocyte, T-Lymphocytes, Team-Dumortier, transgenic},
pubstate = {published},
tppubtype = {article}
}
Monneaux F, Muller S
Laboratory protocols for the identification of Th cell epitopes on self-antigens in mice with systemic autoimmune diseases Journal Article
In: Journal of Immunological Methods, vol. 244, no. 1-2, pp. 195–204, 2000, ISSN: 0022-1759.
Abstract | Links | BibTeX | Tags: Animals, Antigen Presentation, Antigen-Presenting Cells, Autoantigens, B-Lymphocytes, Coculture Techniques, Epitopes, Female, Flow Cytometry, I2CT, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Lymphocyte Activation, Mice, Monneaux, Ribonucleoproteins, Small Nuclear, Systemic, T-Lymphocyte, Team-Dumortier, Th1 Cells, Th2 Cells
@article{monneaux_laboratory_2000,
title = {Laboratory protocols for the identification of Th cell epitopes on self-antigens in mice with systemic autoimmune diseases},
author = {F Monneaux and S Muller},
doi = {10.1016/s0022-1759(00)00256-8},
issn = {0022-1759},
year = {2000},
date = {2000-10-01},
journal = {Journal of Immunological Methods},
volume = {244},
number = {1-2},
pages = {195--204},
abstract = {T cells play a critical role in both the immunological and clinical manifestations of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). Although in normal mice multiple T cell epitopes have been characterized in several self-proteins, there is little information on the fine specificity of autoreactive T cells in lupus model mice and humans. In SLE-prone mice and humans, the only Th cell epitopes identified at the molecular level in self-antigens concern histones and nucleosomes, and the 70-kD U1-snRNP protein. T cell characterization in certain autoimmune mice such as MRL lpr/lpr and NZB/NZW mice has been largely impaired by their hyporesponsiveness in response to mitogen and minimal IL-2 secretion. In addition, MRL lpr/lpr mice also develop lymphadenopathy characterized by the progressive accumulation of functionally immature CD4(-) CD8(-) T cells. It is therefore important to optimize the methods used to measure T cell proliferation and cytokine production ex vivo in order to identify minimal activation in the presence of appropriate antigen. The protocol described in this article has been used for identifying in young MRL lpr/lpr and NZB/NZW mice a CD4(+) T cell epitope in the murine 70-kD U1-RNP protein.},
keywords = {Animals, Antigen Presentation, Antigen-Presenting Cells, Autoantigens, B-Lymphocytes, Coculture Techniques, Epitopes, Female, Flow Cytometry, I2CT, Inbred MRL lpr, Inbred NZB, Lupus Erythematosus, Lymphocyte Activation, Mice, Monneaux, Ribonucleoproteins, Small Nuclear, Systemic, T-Lymphocyte, Team-Dumortier, Th1 Cells, Th2 Cells},
pubstate = {published},
tppubtype = {article}
}