Publications
2017
Nehmar Ramzi, Alsaleh Ghada, Voisin Benjamin, Flacher Vincent, Mariotte Alexandre, Saferding Victoria, Puchner Antonia, Niederreiter Birgit, Vandamme Thierry, Schabbauer Gernot, Kastner Philippe, Chan Susan, Kirstetter Peggy, Holcmann Martin, Mueller Christopher, Sibilia Jean, Bahram Seiamak, Blüml Stephan, Georgel Philippe
Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis Journal Article
In: Arthritis & Rheumatology (Hoboken, N.J.), vol. 69, no. 11, pp. 2124–2135, 2017, ISSN: 2326-5205.
Abstract | Links | BibTeX | Tags: Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha
@article{nehmar_therapeutic_2017,
title = {Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis},
author = {Ramzi Nehmar and Ghada Alsaleh and Benjamin Voisin and Vincent Flacher and Alexandre Mariotte and Victoria Saferding and Antonia Puchner and Birgit Niederreiter and Thierry Vandamme and Gernot Schabbauer and Philippe Kastner and Susan Chan and Peggy Kirstetter and Martin Holcmann and Christopher Mueller and Jean Sibilia and Seiamak Bahram and Stephan Blüml and Philippe Georgel},
doi = {10.1002/art.40225},
issn = {2326-5205},
year = {2017},
date = {2017-01-01},
journal = {Arthritis & Rheumatology (Hoboken, N.J.)},
volume = {69},
number = {11},
pages = {2124--2135},
abstract = {OBJECTIVE: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. This study was undertaken to explore the contribution of PDCs and type I IFNs to RA pathogenesis using various animal models of PDC depletion and to monitor the effect of localized PDC recruitment and activation on joint inflammation and bone damage.
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.},
keywords = {Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.
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}
}
Hess E, Duheron V, Decossas M, Lezot F, Berdal A, Chea S, Golub R, Bosisio M R, Bridal S L, Choi Y, Yagita H, Mueller C G
RANKL induces organized lymph node growth by stromal cell proliferation Journal Article
In: Journal of Immunology, vol. 188, no. 1550-6606 (Electronic), pp. 1245–1254, 2012.
Abstract | Links | BibTeX | Tags: Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Proliferation, Chemokine CCL19, Chemokine CXCL13, chemokines, CXCL13, cytology, development, Growth, growth & development, Hair, hair follicle, Homeostasis, Human, Immune System, Immunization, ligand, LYMPH, LYMPH NODE, Lymph Nodes, Mice, mouse, physiology, plasticity, Proliferation, Protein, rank, RANK ligand, Regulation, Secondary, Stromal Cells, Team-Mueller, transgenic, VCAM1
@article{hess_rankl_2012,
title = {RANKL induces organized lymph node growth by stromal cell proliferation},
author = {E Hess and V Duheron and M Decossas and F Lezot and A Berdal and S Chea and R Golub and M R Bosisio and S L Bridal and Y Choi and H Yagita and C G Mueller},
doi = {10.4049/jimmunol.1101513},
year = {2012},
date = {2012-01-01},
journal = {Journal of Immunology},
volume = {188},
number = {1550-6606 (Electronic)},
pages = {1245--1254},
abstract = {RANK and its ligand RANKL play important roles in the development and regulation of the immune system. We show that mice transgenic for Rank in hair follicles display massive postnatal growth of skin-draining lymph nodes. The proportions of hematopoietic and nonhematopoietic stromal cells and their organization are maintained, with the exception of an increase in B cell follicles. The hematopoietic cells are not activated and respond to immunization by foreign Ag and adjuvant. We demonstrate that soluble RANKL is overproduced from the transgenic hair follicles and that its neutralization normalizes lymph node size, inclusive area, and numbers of B cell follicles. Reticular fibroblastic and vascular stromal cells, important for secondary lymphoid organ formation and organization, express RANK and undergo hyperproliferation, which is abrogated by RANKL neutralization. In addition, they express higher levels of CXCL13 and CCL19 chemokines, as well as MAdCAM-1 and VCAM-1 cell-adhesion molecules. These findings highlight the importance of tissue-derived cues for secondary lymphoid organ homeostasis and identify RANKL as a key molecule for controlling the plasticity of the immune system},
keywords = {Animals, Cell Adhesion, Cell Adhesion Molecules, Cell Proliferation, Chemokine CCL19, Chemokine CXCL13, chemokines, CXCL13, cytology, development, Growth, growth & development, Hair, hair follicle, Homeostasis, Human, Immune System, Immunization, ligand, LYMPH, LYMPH NODE, Lymph Nodes, Mice, mouse, physiology, plasticity, Proliferation, Protein, rank, RANK ligand, Regulation, Secondary, Stromal Cells, Team-Mueller, transgenic, VCAM1},
pubstate = {published},
tppubtype = {article}
}
2011
Duheron V, Hess E, Duval M, Decossas M, Castaneda B, Klopper J E, Amoasii L, Barbaroux J B, Williams I R, Yagita H, Penninger J, Choi Y, Lezot F, Groves R, Paus R, Mueller C G
Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit Journal Article
In: Proc.Natl.Acad.Sci.U.S.A, vol. 108, no. 1091-6490 (Electronic), pp. 5342–5347, 2011.
Abstract | Links | BibTeX | Tags: Activation, Animals, Cell Proliferation, Chemistry, cytology, Epidermis, Epithelial Cells, function, Genetics, Growth, Hair, hair follicle, Homeostasis, Immunology, Inbred C57BL, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, Nude, Osteoprotegerin, physiology, Proliferation, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, signaling, Skin, Skin Transplantation, stem, Stem Cells, Team-Mueller, transgenic, TRANSGENIC MICE, TRANSPLANTATION
@article{duheron_receptor_2011,
title = {Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit},
author = {V Duheron and E Hess and M Duval and M Decossas and B Castaneda and J E Klopper and L Amoasii and J B Barbaroux and I R Williams and H Yagita and J Penninger and Y Choi and F Lezot and R Groves and R Paus and C G Mueller},
doi = {10.1073/pnas.1013054108},
year = {2011},
date = {2011-03-01},
journal = {Proc.Natl.Acad.Sci.U.S.A},
volume = {108},
number = {1091-6490 (Electronic)},
pages = {5342--5347},
abstract = {Receptor activator of NF-kappaB (RANK), known for controlling bone mass, has been recognized for its role in epithelial cell activation of the mammary gland. Because bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages, we have addressed the function of RANK in the hair follicle and the epidermis. Here, we show that mice deficient in RANK ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. However, transgenic mice overexpressing RANK in the hair follicle or administration of recombinant RANKL both activate the hair cycle and epidermal growth. RANK is expressed by the hair follicle germ and bulge stem cells and the epidermal basal cells, cell types implicated in the renewal of the epidermo-pilosebaceous unit. RANK signaling is dispensable for the formation of the stem cell compartment and the inductive hair follicle mesenchyme, and the hair cycle can be rescued by Rankl knockout skin transplantation onto nude mice. RANKL is actively transcribed by the hair follicle at initiation of its growth phase, providing a mechanism for stem cell RANK engagement and hair-cycle entry. Thus, RANK-RANKL regulates hair renewal and epidermal homeostasis and provides a link between these two activities},
keywords = {Activation, Animals, Cell Proliferation, Chemistry, cytology, Epidermis, Epithelial Cells, function, Genetics, Growth, Hair, hair follicle, Homeostasis, Immunology, Inbred C57BL, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, Nude, Osteoprotegerin, physiology, Proliferation, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, signaling, Skin, Skin Transplantation, stem, Stem Cells, Team-Mueller, transgenic, TRANSGENIC MICE, TRANSPLANTATION},
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
Durand Stéphanie H, Flacher Vincent, Roméas Annick, Carrouel Florence, Colomb Evelyne, Vincent Claude, Magloire Henry, Couble Marie-Lise, Bleicher Françoise, Staquet Marie-Jeanne, Lebecque Serge, Farges Jean-Christophe
In: Journal of Immunology (Baltimore, Md.: 1950), vol. 176, no. 5, pp. 2880–2887, 2006, ISSN: 0022-1767.
Abstract | Links | BibTeX | Tags: Activation, Analysis, bacteria, Biosynthesis, BLOOD, Blood Vessels, Cell Differentiation, Cells, Chemistry, chemokines, COLLAGEN, Cultured, CXCL10, cytology, Dendritic Cells, DENTAL PULP, Dentin, development, Down-Regulation, Expression, extracellular, EXTRACELLULAR MATRIX, Extracellular Matrix Proteins, function, Gene, Gene Expression, Genes, Genetics, Gram-Positive Bacteria, Human, Humans, IMMATURE, Immunology, IN VITRO, In vivo, Innate immune response, lipopolysaccharide, Lipopolysaccharides, metabolism, migration, Odontoblasts, Organ Culture Techniques, Pharmacology, physiology, PRODUCTION, Protein, Proteins, Receptor, recognition, synthesis, Team-Mueller, Teichoic Acids, TLR7, Toll-Like Receptor 2, Up-Regulation
@article{durand_lipoteichoic_2006,
title = {Lipoteichoic acid increases TLR and functional chemokine expression while reducing dentin formation in in vitro differentiated human odontoblasts},
author = {Stéphanie H Durand and Vincent Flacher and Annick Roméas and Florence Carrouel and Evelyne Colomb and Claude Vincent and Henry Magloire and Marie-Lise Couble and Françoise Bleicher and Marie-Jeanne Staquet and Serge Lebecque and Jean-Christophe Farges},
doi = {10.4049/jimmunol.176.5.2880},
issn = {0022-1767},
year = {2006},
date = {2006-03-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {176},
number = {5},
pages = {2880--2887},
abstract = {Gram-positive bacteria entering the dentinal tissue during the carious process are suspected to influence the immune response in human dental pulp. Odontoblasts situated at the pulp/dentin interface are the first cells encountered by these bacteria and therefore could play a crucial role in this response. In the present study, we found that in vitro-differentiated odontoblasts constitutively expressed the pattern recognition receptor TLR1-6 and 9 genes but not TLR7, 8, and 10. Furthermore, lipoteichoic acid (LTA), a wall component of Gram-positive bacteria, triggered the activation of the odontoblasts. LTA up-regulated the expression of its own receptor TLR2, as well as the production of several chemokines. In particular, an increased amount of CCL2 and CXCL10 was detected in supernatants from LTA-stimulated odontoblasts, and those supernatants augmented the migration of immature dendritic cells in vitro compared with controls. Clinical relevance of these observations came from immunohistochemical analysis showing that CCL2 was expressed in vivo by odontoblasts and blood vessels present under active carious lesions but not in healthy dental pulps. In contrast with this inflammatory response, gene expression of major dentin matrix components (type I collagen, dentin sialophosphoprotein) and TGF-beta1 was sharply down-regulated in odontoblasts by LTA. Taken together, these data suggest that odontoblasts activated through TLR2 by Gram-positive bacteria LTA are able to initiate an innate immune response by secreting chemokines that recruit immature dendritic cells while down-regulating their specialized functions of dentin matrix synthesis and mineralization.},
keywords = {Activation, Analysis, bacteria, Biosynthesis, BLOOD, Blood Vessels, Cell Differentiation, Cells, Chemistry, chemokines, COLLAGEN, Cultured, CXCL10, cytology, Dendritic Cells, DENTAL PULP, Dentin, development, Down-Regulation, Expression, extracellular, EXTRACELLULAR MATRIX, Extracellular Matrix Proteins, function, Gene, Gene Expression, Genes, Genetics, Gram-Positive Bacteria, Human, Humans, IMMATURE, Immunology, IN VITRO, In vivo, Innate immune response, lipopolysaccharide, Lipopolysaccharides, metabolism, migration, Odontoblasts, Organ Culture Techniques, Pharmacology, physiology, PRODUCTION, Protein, Proteins, Receptor, recognition, synthesis, Team-Mueller, Teichoic Acids, TLR7, Toll-Like Receptor 2, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}