Publications
2018
Muller Quentin, Beaudet Marie-Josée, Serres-Bérard Thiéry De, Bellenfant Sabrina, Flacher Vincent, Berthod François
Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells Journal Article
In: Acta Biomaterialia, vol. 82, pp. 93–101, 2018, ISSN: 1878-7568.
Abstract | Links | BibTeX | Tags: atopic dermatitis, Axonal migration, Biological, Canada, Cells, CGRP, Chemistry, COLLAGEN, Culture, Dermatitis, development, disease, Endothelial Cells, ENDOTHELIAL-CELLS, Epidermis, Expression, Fibroblast, Fibroblasts, function, Human, Humans, Immune System, Immunology, immunopathology, IN VITRO, Induced Pluripotent Stem Cells, inflammation, INNERVATION, Maturation, migration, Models, mouse, murine, Nerve, Neurites, Neurogenic Inflammation, Neurons, NEUROPEPTIDE, Neuropeptides, physiopathology, Pluripotent Stem Cells, Psoriasis, SCHWANN CELLS, Sensory Receptor Cells, Skin, skin disease, Skin Diseases, stem, Stem Cells, SUBSTANCE, SUBSTANCE P, Team-Mueller, Tissue Engineering, TRPV1
@article{muller_development_2018,
title = {Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells},
author = {Quentin Muller and Marie-Josée Beaudet and Thiéry De Serres-Bérard and Sabrina Bellenfant and Vincent Flacher and François Berthod},
doi = {10.1016/j.actbio.2018.10.011},
issn = {1878-7568},
year = {2018},
date = {2018-01-01},
journal = {Acta Biomaterialia},
volume = {82},
pages = {93--101},
abstract = {Cutaneous innervation is increasingly recognized as a major element of skin physiopathology through the neurogenic inflammation driven by neuropeptides that are sensed by endothelial cells and the immune system. To investigate this process in vitro, models of innervated tissue-engineered skin (TES) were developed, yet exclusively with murine sensory neurons extracted from dorsal root ganglions. In order to build a fully human model of innervated TES, we used induced pluripotent stem cells (iPSC) generated from human skin fibroblasts. Nearly 100% of the iPSC differentiated into sensory neurons were shown to express the neuronal markers BRN3A and β3-tubulin after 19 days of maturation. In addition, these cells were also positive to TRPV1 and neurofilament M, and some of them expressed Substance P, TrkA and TRPA1. When stimulated with molecules inducing neuropeptide release, iPSC-derived neurons released Substance P and CGRP, both in conventional monolayer culture and after seeding in a 3D fibroblast-populated collagen sponge model. Schwann cells, the essential partners of neurons for function and axonal migration, were also successfully differentiated from human iPSC as shown by their expression of the markers S100, GFAP, p75 and SOX10. When cultured for one additional month in the TES model, iPSC-derived neurons seeded at the bottom of the sponge formed a network of neurites spanning the whole TES up to the epidermis, but only when combined with mouse or iPSC-derived Schwann cells. This unique model of human innervated TES should be highly useful for the study of cutaneous neuroinflammation. STATEMENT OF SIGNIFICANCE: The purpose of this work was to develop in vitro an innovative fully human tissue-engineered skin enabling the investigation of the influence of cutaneous innervation on skin pathophysiology. To reach that aim, neurons were differentiated from human induced pluripotent stem cells (iPSCs) generated from normal human skin fibroblasts. This innervated tissue-engineered skin model will be the first one to show iPSC-derived neurons can be successfully used to build a 3D nerve network in vitro. Since innervation has been recently recognized to play a central role in many human skin diseases, such as psoriasis and atopic dermatitis, this construct promises to be at the forefront to model these diseases while using patient-derived cells.},
keywords = {atopic dermatitis, Axonal migration, Biological, Canada, Cells, CGRP, Chemistry, COLLAGEN, Culture, Dermatitis, development, disease, Endothelial Cells, ENDOTHELIAL-CELLS, Epidermis, Expression, Fibroblast, Fibroblasts, function, Human, Humans, Immune System, Immunology, immunopathology, IN VITRO, Induced Pluripotent Stem Cells, inflammation, INNERVATION, Maturation, migration, Models, mouse, murine, Nerve, Neurites, Neurogenic Inflammation, Neurons, NEUROPEPTIDE, Neuropeptides, physiopathology, Pluripotent Stem Cells, Psoriasis, SCHWANN CELLS, Sensory Receptor Cells, Skin, skin disease, Skin Diseases, stem, Stem Cells, SUBSTANCE, SUBSTANCE P, Team-Mueller, Tissue Engineering, TRPV1},
pubstate = {published},
tppubtype = {article}
}
2016
Cordeiro Olga G, Chypre Mélanie, Brouard Nathalie, Rauber Simon, Alloush Farouk, Romera-Hernandez Monica, Bénézech Cécile, Li Zhi, Eckly Anita, Coles Mark C, Rot Antal, Yagita Hideo, Léon Catherine, Ludewig Burkhard, Cupedo Tom, Lanza François, Mueller Christopher G
Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL Journal Article
In: PloS One, vol. 11, no. 3, pp. e0151848, 2016, ISSN: 1932-6203.
Abstract | Links | BibTeX | Tags: Activation, Animals, Cells, Cultured, Endothelial Cells, ENDOTHELIAL-CELLS, Expression, Fibronectins, Immunization, Immunology, immunopathology, Inbred C57BL, infection, ligand, LYMPH, LYMPH NODE, Lymph Nodes, lymphoid organs, Lymphotoxin, Lymphotoxin-beta, Mice, murine, NF-kappaB, Platelet Membrane Glycoprotein IIb, PLATELETS, PROGENITORS, rank, RANK ligand, Receptor, Secondary, Signal Transduction, signaling, SINUS, Team-Mueller
@article{cordeiro_integrin-alpha_2016,
title = {Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL},
author = {Olga G Cordeiro and Mélanie Chypre and Nathalie Brouard and Simon Rauber and Farouk Alloush and Monica Romera-Hernandez and Cécile Bénézech and Zhi Li and Anita Eckly and Mark C Coles and Antal Rot and Hideo Yagita and Catherine Léon and Burkhard Ludewig and Tom Cupedo and François Lanza and Christopher G Mueller},
doi = {10.1371/journal.pone.0151848},
issn = {1932-6203},
year = {2016},
date = {2016-01-01},
journal = {PloS One},
volume = {11},
number = {3},
pages = {e0151848},
abstract = {Microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (LEC) population. Particularly LECs of secondary lymphoid organs are exposed to different cell types and immune stimuli. However, our understanding of the nature of LEC activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node subset of LECs, residing in medullary, cortical and subcapsular sinuses. In the subcapsular sinus, the floor but not the ceiling layer expresses the integrin, being excluded from ACKR4+ LECs but overlapping with MAdCAM-1 expression. ITGA2b expression increases in response to immunization, raising the possibility that heterogeneous ITGA2b levels reflect variation in exposure to activation signals. We show that alterations of the level of receptor activator of NF-κB ligand (RANKL), by overexpression, neutralization or deletion from stromal marginal reticular cells, affected the proportion of ITGA2b+ LECs. Lymph node LECs but not peripheral LECs express RANK. In addition, we found that lymphotoxin-β receptor signaling likewise regulated the proportion of ITGA2b+ LECs. These findings demonstrate that stromal reticular cells activate LECs via RANKL and support the action of hematopoietic cell-derived lymphotoxin.},
keywords = {Activation, Animals, Cells, Cultured, Endothelial Cells, ENDOTHELIAL-CELLS, Expression, Fibronectins, Immunization, Immunology, immunopathology, Inbred C57BL, infection, ligand, LYMPH, LYMPH NODE, Lymph Nodes, lymphoid organs, Lymphotoxin, Lymphotoxin-beta, Mice, murine, NF-kappaB, Platelet Membrane Glycoprotein IIb, PLATELETS, PROGENITORS, rank, RANK ligand, Receptor, Secondary, Signal Transduction, signaling, SINUS, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
2015
Mairhofer David G, Ortner Daniela, Tripp Christoph H, Schaffenrath Sandra, Fleming Viktor, Heger Lukas, Komenda Kerstin, Reider Daniela, Dudziak Diana, Chen Suzie, Becker Jürgen C, Flacher Vincent, Stoitzner Patrizia
Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model Journal Article
In: The Journal of Investigative Dermatology, vol. 135, no. 11, pp. 2785–2793, 2015, ISSN: 1523-1747.
Abstract | Links | BibTeX | Tags: Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity
@article{mairhofer_impaired_2015,
title = {Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model},
author = {David G Mairhofer and Daniela Ortner and Christoph H Tripp and Sandra Schaffenrath and Viktor Fleming and Lukas Heger and Kerstin Komenda and Daniela Reider and Diana Dudziak and Suzie Chen and Jürgen C Becker and Vincent Flacher and Patrizia Stoitzner},
doi = {10.1038/jid.2015.241},
issn = {1523-1747},
year = {2015},
date = {2015-11-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {11},
pages = {2785--2793},
abstract = {Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.},
keywords = {Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity},
pubstate = {published},
tppubtype = {article}
}
Haid Bernhard, Schlögl David E, Hermann Martin, Tripp Christoph H, Stoitzner Patrizia, Romani Nikolaus, Flacher Vincent
Langerhans cells in the sebaceous gland of the murine skin Journal Article
In: Experimental Dermatology, vol. 24, no. 11, pp. 899–901, 2015, ISSN: 1600-0625.
Links | BibTeX | Tags: Animals, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermis, Inbred BALB C, Inbred C57BL, Langerhans Cells, Langerin, Letter, Mice, murine, pilosebaceous unit, sebaceous gland, Sebaceous Glands, Skin, Team-Mueller
@article{haid_langerhans_2015,
title = {Langerhans cells in the sebaceous gland of the murine skin},
author = {Bernhard Haid and David E Schlögl and Martin Hermann and Christoph H Tripp and Patrizia Stoitzner and Nikolaus Romani and Vincent Flacher},
doi = {10.1111/exd.12803},
issn = {1600-0625},
year = {2015},
date = {2015-11-01},
journal = {Experimental Dermatology},
volume = {24},
number = {11},
pages = {899--901},
keywords = {Animals, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermis, Inbred BALB C, Inbred C57BL, Langerhans Cells, Langerin, Letter, Mice, murine, pilosebaceous unit, sebaceous gland, Sebaceous Glands, Skin, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
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}
}
2012
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 Journal Article
In: Journal of Immunology, vol. 188, no. 1550-6606 (Electronic), pp. 2146–2155, 2012.
Abstract | BibTeX | Tags: 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}
}
2010
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}
}
2009
Bosisio M R, Maisonneuve C, Gregoire S, Kettaneh A, Mueller C G, Bridal S L
Ultrasound biomicroscopy: a powerful tool probing murine lymph node size in vivo Journal Article
In: Ultrasound Med.Biol., vol. 35, no. 1879-291X (Electronic), pp. 1209–1216, 2009.
Abstract | BibTeX | Tags: Acoustic, Animals, Axilla, cancer, Cell Count, Female, Graft Rejection, Hyperplasia, immunodeficiency, In vivo, Inbred C57BL, inflammation, LYMPH, LYMPH NODE, Lymph Nodes, Male, methods, Mice, Microscopy, murine, Observer Variation, pathology, SKIN GRAFT, Skin Transplantation, Team-Mueller, transgenic, TRANSGENIC MICE, ultrasonography
@article{bosisio_ultrasound_2009,
title = {Ultrasound biomicroscopy: a powerful tool probing murine lymph node size in vivo},
author = {M R Bosisio and C Maisonneuve and S Gregoire and A Kettaneh and C G Mueller and S L Bridal},
year = {2009},
date = {2009-07-01},
journal = {Ultrasound Med.Biol.},
volume = {35},
number = {1879-291X (Electronic)},
pages = {1209--1216},
abstract = {Invasive cell-counting in lymph node (LN) is the current reference to assess LN changes due to inflammation, immunodeficiency and cancer in murine models. This work evaluates whether ultrasound biomicroscopy (UBM) can measure LN size alterations noninvasively for a large range of sizes (0.1 mm3 to 22 mm3). Correlation was assessed (rho = 0.91, p textless 0.0001) between invasive cell count and LN volume estimated with UBM (24, 2 to 28-week-old, C57BL/6 mice; 13 same-strain, transgenic mice presenting LN hyperplasia). UBM LN modification screening was applied in a skin-graft rejection model and compared with cell-counting (15 mice). UBM LN-size follow-up with fine temporal sampling was demonstrated from 9 d of age (minimum area 0.13 mm2). Reliability (intraclass correlation coefficient [ICC] textgreater 0.84) and variability of UBM evaluations compared favourably with invasive cell count. UBM provides a noninvasive alternative to cell-counting in mice for early detection and longitudinal screening of LN modifications. This can enable significant reduction in the number of mice and exploration of LNs that would be too small to dissect for cell count},
keywords = {Acoustic, Animals, Axilla, cancer, Cell Count, Female, Graft Rejection, Hyperplasia, immunodeficiency, In vivo, Inbred C57BL, inflammation, LYMPH, LYMPH NODE, Lymph Nodes, Male, methods, Mice, Microscopy, murine, Observer Variation, pathology, SKIN GRAFT, Skin Transplantation, Team-Mueller, transgenic, TRANSGENIC MICE, ultrasonography},
pubstate = {published},
tppubtype = {article}
}
2008
Tripp Christoph H, Haid Bernhard, Flacher Vincent, Sixt Michael, Peter Hannes, Farkas Julia, Gschwentner Robert, Sorokin Lydia, Romani Nikolaus, Stoitzner Patrizia
The lymph vessel network in mouse skin visualised with antibodies against the hyaluronan receptor LYVE-1 Journal Article
In: Immunobiology, vol. 213, no. 9-10, pp. 715–728, 2008, ISSN: 0171-2985.
Abstract | Links | BibTeX | Tags: anatomy & histology, Animals, Antibodies, antibody, BLOOD, Blood Vessels, CD31, Cell Movement, Culture, cytology, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, DERMIS, EAR, electron microscopy, ENDOTHELIUM, Expression, GLYCOPROTEIN, Glycoproteins, hyaluronan, imiquimod, Immunology, Immunotherapy, In vivo, Inbred BALB C, Inbred C57BL, Langerhans Cells, ligand, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, LYVE-1, Membrane Transport Proteins, metabolism, MHC, Mice, migration, mouse, murine, physiology, priming, Protein, Receptor, Skin, tape stripping, Team-Mueller, tolerance
@article{tripp_lymph_2008,
title = {The lymph vessel network in mouse skin visualised with antibodies against the hyaluronan receptor LYVE-1},
author = {Christoph H Tripp and Bernhard Haid and Vincent Flacher and Michael Sixt and Hannes Peter and Julia Farkas and Robert Gschwentner and Lydia Sorokin and Nikolaus Romani and Patrizia Stoitzner},
doi = {10.1016/j.imbio.2008.07.025},
issn = {0171-2985},
year = {2008},
date = {2008-01-01},
journal = {Immunobiology},
volume = {213},
number = {9-10},
pages = {715--728},
abstract = {Langerhans cells and dermal dendritic cells migrate to the draining lymph nodes through dermal lymphatic vessels. They do so in the steady-state and under inflammatory conditions. Peripheral T cell tolerance or T cell priming, respectively, are the consequences of migration. The nature of dendritic cell-containing vessels was mostly defined by electron microscopy or by their lack of blood endothelial markers. Selective markers for murine lymph endothelium were hitherto rare or not available. Here, we utilised recently developed antibodies against the murine hyaluronan receptor, LYVE-1, to study the lymph vessel network in mouse skin in more detail. In hairless skin from the ears, lymph vessels were spread out in a horizontal plane. They formed anastomoses, and they possessed frequent blind endings that were occasionally open. Lymph vessels were wider than blood vessels, which were identified by their strong CD31 expression. In body wall skin LYVE-1 reactive vessels did not extend laterally but they dived straight down into the deeper dermis. There, they are connected to each other and formed a network similar to ear skin. The number and width of lymph vessels did not grossly change upon inflammatory stimuli such as skin explant culture or tape stripping. There were also no marked changes in caliber in response to the TLR 7/8 ligand Imiquimod. Double-labelling experiments of cultured skin showed that most of the strongly cell surface MHC II-expressing (i.e. activated) dendritic cells were confined to the lymph vessels. Langerin/CD207(+) cells within this population appeared later than dermal dendritic cells, i.e. langerin-negative cells. Comparable results were obtained after stimulating the skin in vivo with the TLR 7/8 ligand Imiquimod or by tape stripping. In untreated skin (i.e. steady state) a few MHC II(+) and Langerin/CD207(+) cells, presumably migrating skin dendritic cells including epidermal Langerhans cells, were consistently observed within the lymph vessels. The novel antibody reagents may serve as important tools to further study the dendritic cell traffic in the skin under physiological conditions as well as in conditions of adoptive dendritic cell transfer in immunotherapy.},
keywords = {anatomy & histology, Animals, Antibodies, antibody, BLOOD, Blood Vessels, CD31, Cell Movement, Culture, cytology, Dendritic Cells, DERMAL DENDRITIC CELLS, DERMATOLOGY, DERMIS, EAR, electron microscopy, ENDOTHELIUM, Expression, GLYCOPROTEIN, Glycoproteins, hyaluronan, imiquimod, Immunology, Immunotherapy, In vivo, Inbred BALB C, Inbred C57BL, Langerhans Cells, ligand, LYMPH, LYMPH NODE, Lymph Nodes, LYMPHATIC VESSEL, Lymphatic Vessels, LYVE-1, Membrane Transport Proteins, metabolism, MHC, Mice, migration, mouse, murine, physiology, priming, Protein, Receptor, Skin, tape stripping, Team-Mueller, tolerance},
pubstate = {published},
tppubtype = {article}
}
2006
Barbaroux Jean-Baptiste, Kwan Wing-Hong, Allam Jean-Pierre, Novak Natalija, Bieber Thomas, Fridman Wolf H, Groves Richard, Mueller Chris G
Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell-like dendritic cells from M-CSF-conditioned precursors Journal Article
In: The Journal of Investigative Dermatology, vol. 126, no. 1, pp. 114–120, 2006, ISSN: 0022-202X.
Abstract | Links | BibTeX | Tags: Antigens, C-Type, Carrier Proteins, CC, CCR6, CD, CD1, CD34, Cell Differentiation, Chemokine, Chemokine CCL20, chemokines, Cytokines, DERMIS, FRANZ, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Humans, IL-4, Interleukin-4, Langerhans Cells, Lectins, Lipopolysaccharide Receptors, M-CSF, Macrophage Colony-Stimulating Factor, Macrophage Inflammatory Proteins, Mannose-Binding Lectins, Membrane Glycoproteins, murine, RANK ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Surface, Team-Mueller, TNF ALPHA, Tumor Necrosis Factor-alpha
@article{barbaroux_tumor_2006,
title = {Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell-like dendritic cells from M-CSF-conditioned precursors},
author = {Jean-Baptiste Barbaroux and Wing-Hong Kwan and Jean-Pierre Allam and Natalija Novak and Thomas Bieber and Wolf H Fridman and Richard Groves and Chris G Mueller},
doi = {10.1038/sj.jid.5700023},
issn = {0022-202X},
year = {2006},
date = {2006-01-01},
journal = {The Journal of Investigative Dermatology},
volume = {126},
number = {1},
pages = {114--120},
abstract = {GM-CSF and transforming growth factor beta (TGFbeta ) are required for the generation of Langerhans cells (LC), members of the dendritic cell (DC) family. Tumor necrosis factor alpha (TNFalpha) and IL-4 can enhance LC differentiation from human monocytes or CD34(+) progenitors. Here, we show that M-CSF-cultured DC precursors derived from CD34(+) progenitors resemble dermal CD14(+) cells and readily convert to LC-like DC in GM-CSF/TGFbeta. The cells express Langerin, CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck granules. TNFalpha and IL-4, added separately or together, have an inhibitory effect on LC differentiation. Cells differentiated in the presence of IL-4 and TNFalpha express low levels of CCR7. This suggests that M-CSF-conditioned DC precursors retain the capacity to efficiently undergo a differentiation program, giving rise to LC-like DC solely through the effect of GM-CSF and TGFbeta.},
keywords = {Antigens, C-Type, Carrier Proteins, CC, CCR6, CD, CD1, CD34, Cell Differentiation, Chemokine, Chemokine CCL20, chemokines, Cytokines, DERMIS, FRANZ, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Humans, IL-4, Interleukin-4, Langerhans Cells, Lectins, Lipopolysaccharide Receptors, M-CSF, Macrophage Colony-Stimulating Factor, Macrophage Inflammatory Proteins, Mannose-Binding Lectins, Membrane Glycoproteins, murine, RANK ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Surface, Team-Mueller, TNF ALPHA, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}
1997
Mueller C G F, Rissoan M C, Salinas B, Ait-Yahia S, Ravel O, Bridon J M, Briere F, Lebecque S, Liu Y J
Polymerase chain reaction selects a novel disintegrin proteinase from CD40-activated germinal center dendritic cells Journal Article
In: Journal of Experimental Medicine, vol. 186, pp. 655–663, 1997.
BibTeX | Tags: Dendritic Cells, Germinal Center, METALLOPROTEINASE, murine, Team-Mueller
@article{mueller_polymerase_1997-1,
title = {Polymerase chain reaction selects a novel disintegrin proteinase from CD40-activated germinal center dendritic cells},
author = {C G F Mueller and M C Rissoan and B Salinas and S Ait-Yahia and O Ravel and J M Bridon and F Briere and S Lebecque and Y J Liu},
year = {1997},
date = {1997-01-01},
journal = {Journal of Experimental Medicine},
volume = {186},
pages = {655--663},
keywords = {Dendritic Cells, Germinal Center, METALLOPROTEINASE, murine, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}