RNA interference and receptors

@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}

}

@article{voisin_anatomical_2014,

title = {Anatomical distribution analysis reveals lack of Langerin+ dermal dendritic cells in footpads and tail of C57BL/6 mice},

author = {Benjamin Voisin and David Gabriel Mairhofer and Suzie Chen and Patrizia Stoitzner and Christopher George Mueller and Vincent Flacher},

doi = {10.1111/exd.12373},

issn = {1600-0625},

year  = {2014},

date = {2014-01-01},

journal = {Experimental Dermatology},

volume = {23},

number = {5},

pages = {354--356},

abstract = {Epidermal Langerhans cells (LCs) and dermal dendritic cells (dDCs) capture cutaneous antigens and present them to T-cells in lymph nodes (LNs). The function of LCs and Langerin+ dDCs was extensively studied in the mouse, but their anatomical repartition is unknown. Here, we found LCs in back skin, footpads and tail skin of C57BL/6, BALB/c, 129/Sv and CBA/J mice. Langerin+ dDCs were readily observed in back skin of all strains, but only in footpads and tail of BALB/c and CBA/J mice. Similarly, while LCs were equally present in all LNs and strains, Langerin+ dDCs were found in popliteal LNs (draining footpads) only in BALB/c and CBA/J mice. The sciatic LNs, which we identified as the major tail-draining lymphoid organ, were devoid of Langerin+ dDCs in all strains. Thus, functionally different DCs reside in different skin areas, with variations among mouse strains, implying a potential impact on the cutaneous immune reaction.},

keywords = {Analysis, Animals, Antigen, Antigens, C-Type, CD, CD11c Antigen, Cell Adhesion Molecules, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cell Adhesion Molecule, footpad skin, function, Hindlimb, immunopathology, Inbred BALB C, Inbred C57BL, Inbred CBA, inflammation, Integrin alpha Chains, Langerhans Cells, Lectins, Letter, Leukocyte Common Antigens, LYMPH, LYMPH NODE, Lymph Nodes, Mannose-Binding Lectins, Mice, mouse, Neoplasm, Skin, skin-draining lymph nodes, Surface, T CELLS, T-CELLS, Tail, tail skin, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{quintin_drosophila_2013b,

title = {The Drosophila Toll pathway controls but does not clear Candida glabrata infections},

author = {Jessica Quintin and Joelle Asmar and Alexey A Matskevich and Marie-Céline Lafarge and Dominique Ferrandon},

doi = {10.4049/jimmunol.1201861},

issn = {1550-6606},

year  = {2013},

date = {2013-03-01},

journal = {J. Immunol.},

volume = {190},

number = {6},

pages = {2818--2827},

abstract = {The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host.},

keywords = {Adaptor Proteins, Animal, Animals, Antigens, Candida glabrata, Candidiasis, Cells, Cultured, Differentiation, Disease Models, ferrandon, Immunologic, M3i, Phagocytosis, Receptors, Signal Transducing, Signal Transduction, Toll-Like Receptors, Virulence},

pubstate = {published},

tppubtype = {article}

}

@article{ayyaz_negative_2013b,

title = {A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus},

author = {Arshad Ayyaz and Philippe Giammarinaro and Samuel Liégeois and Matthieu Lestradet and Dominique Ferrandon},

doi = {10.1016/j.imbio.2012.07.027},

issn = {1878-3279},

year  = {2013},

date = {2013-01-01},

journal = {Immunobiology},

volume = {218},

number = {4},

pages = {635--644},

abstract = {Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development.},

keywords = {Adaptor Proteins, Animal, Animals, Antigens, Differentiation, Disease Models, ferrandon, Immunity, Immunologic, Innate, Intestinal Diseases, M3i, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{romani_targeting_2012,

title = {Targeting skin dendritic cells to improve intradermal vaccination},

author = {N Romani and V Flacher and C H Tripp and F Sparber and S Ebner and P Stoitzner},

doi = {10.1007/82_2010_118},

issn = {0070-217X},

year  = {2012},

date = {2012-01-01},

journal = {Current Topics in Microbiology and Immunology},

volume = {351},

pages = {113--138},

abstract = {Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(neg), and dermal langerin(+) dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerin(neg) dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14(+) dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge.},

keywords = {Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases},

pubstate = {published},

tppubtype = {article}

}

@article{venturelli_antibody_2011,

title = {Antibody covalent immobilization on carbon nanotubes and assessment of antigen binding},

author = {Enrica Venturelli and Chiara Fabbro and Olivier Chaloin and Cécilia Ménard-Moyon and Cristian R Smulski and Tatiana Da Ros and Kostas Kostarelos and Maurizio Prato and Alberto Bianco},

doi = {10.1002/smll.201100137},

issn = {1613-6829},

year  = {2011},

date = {2011-08-01},

journal = {Small (Weinheim an Der Bergstrasse, Germany)},

volume = {7},

number = {15},

pages = {2179--2187},

abstract = {Controlling the covalent bonding of antibodies onto functionalized carbon nanotubes is a key step in the design and preparation of nanotube-based conjugates for targeting cancer cells. For this purpose, an anti-MUC1 antibody (Ab) is linked to both multi-walled (MWCNTs) and double-walled carbon nanotubes (DWCNTs) using different synthetic strategies. The presence of the Ab attached to the nanotubes is confirmed by gel electrophoresis and thermogravimetric analysis. Most importantly, molecular recognition of the antigen by surface plasmon resonance is able to determine similar Ab binding capacities for both Ab-DWCNTs and Ab-MWCNTs. These results are very relevant for the design of future receptor-targeting strategies using chemically functionalized carbon nanotubes.},

keywords = {Antibodies, Antigens, carbon, I2CT, Immobilized, Mucin-1, nanotechnology, Nanotubes, Protein Binding, Team-Bianco, Thermogravimetry},

pubstate = {published},

tppubtype = {article}

}

@article{banchet-cadeddu_stimulating_2011,

title = {The stimulating adventure of KRN 7000},

author = {Aline Banchet-Cadeddu and Eric Hénon and Manuel Dauchez and Jean-Hugues Renault and Fanny Monneaux and Arnaud Haudrechy},

doi = {10.1039/c0ob00975j},

issn = {1477-0539},

year  = {2011},

date = {2011-01-01},

journal = {Organic & Biomolecular Chemistry},

volume = {9},

number = {9},

pages = {3080--3104},

abstract = {Associated with the CD1d protein, KRN 7000, a potent synthetic α-galactosylceramide, is known to activate the invariant NKT immune cells. This stimulation then leads to the production of different cytokines modulating a T(H)1/T(H)2 immune response balance involved in protection against several pathologies such as autoimmune diseases and cancers. Various efforts have been made toward the synthesis of simple and more functionalized analogues in order to selectively induce T(H)1 or T(H)2-type cytokine production. Since the discovery of KRN 7000, structure-activity relationships, crystallographic and modelling studies have pointed to the potential of several GalCer analogues in term of selective bioactivity, and have highlighted interesting elements in order to better understand the recognition and activation mechanisms of immune iNKT cells. By presenting an up-to-date library of analogues, collecting recent breakthroughs done in crystallography and molecular modelling, and relating them to the available biological results, we hope that this review will highlight and help the scientific community in their KRN research.},

keywords = {Adjuvants, Animals, Antigen, Antigens, CD1d, Galactosylceramides, Helper-Inducer, Humans, I2CT, Immunologic, Monneaux, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{noordegraaf_functional_2010,

title = {Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity},

author = {Madelon Noordegraaf and Vincent Flacher and Patrizia Stoitzner and Björn E Clausen},

doi = {10.1038/jid.2010.223},

issn = {1523-1747},

year  = {2010},

date = {2010-12-01},

journal = {The Journal of Investigative Dermatology},

volume = {130},

number = {12},

pages = {2752--2759},

abstract = {The relative roles of Langerhans cells (LC), dermal dendritic cells (DC), and, in particular, the recently discovered Langerin(+) dermal DC subset in the induction and control of contact hypersensitivity (CHS) responses remain controversial. Using an inducible mouse model, in which LC and other Langerin(+) DC can be depleted by injection of diphtheria toxin, we previously reported impaired transport of topically applied antigen to draining lymph nodes and reduced CHS in the absence of all Langerin(+) skin DC. In this study, we demonstrate that mice with a selective depletion of LC exhibit attenuated CHS only upon sensitization with a low hapten dose but not with a high hapten dose. In contrast, when painting a higher concentration of hapten onto the skin, which leads to increased antigen dissemination into the dermis, CHS is still diminished in mice lacking all Langerin(+) skin DC. Taken together, these data suggest that the magnitude of a CHS reaction depends on the number of skin DC, which have access to the hapten, rather than on the presence or absence of a particular skin DC population. LC and (Langerin(+)) dermal DC thus seem to have a redundant function in regulating CHS.},

keywords = {Animal, Animals, Antigen, Antigens, C-Type, CHS, contact, CONTACT HYPERSENSITIVITY, Dendritic Cells, DEPLETION, DERMAL DENDRITIC CELLS, Dermatitis, DERMIS, Diphtheria Toxin, Disease Models, Epidermis, function, Gene Knock-In Techniques, Genetics, Growth, HAPTEN, Haptens, Heparin-binding EGF-like Growth Factor, Hypersensitivity, Immunology, Inbred C57BL, INDUCTION, Intercellular Signaling Peptides and Proteins, LACKING, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Mannose-Binding Lectins, metabolism, Mice, mouse, Mutant Strains, Organ Culture Techniques, pathology, Peptides, Poisons, Protein, Proteins, RESPONSES, signaling, Skin, Surface, Team-Mueller, Toxicity},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{menard-moyon_functionalized_2010,

title = {Functionalized carbon nanotubes for probing and modulating molecular functions},

author = {Cécilia Ménard-Moyon and Kostas Kostarelos and Maurizio Prato and Alberto Bianco},

doi = {10.1016/j.chembiol.2010.01.009},

issn = {1879-1301},

year  = {2010},

date = {2010-02-01},

journal = {Chemistry & Biology},

volume = {17},

number = {2},

pages = {107--115},

abstract = {Carbon nanotubes (CNTs) entered the domain of biological research a few years ago, creating a significant amount of interest due to their extraordinary physicochemical properties. The integration of CNT-based strategies with biology necessitates a multidisciplinary approach that requires competences in the diverse fields of chemistry, physics, and life sciences. In the biomedical domain CNTs are extensively explored as novel drug delivery systems for therapy and diagnosis. Additionally, CNTs can also be designed as new tools for modulation of molecular functions, by directly affecting various biological processes or by interaction with bioactive molecules. The aim of this review is to discuss how CNTs can be exploited as new probes for molecular functions. The different sections illustrate various applications of CNTs, including gene silencing, surface cell interactions via glycoproteins, biosensing, intracellular drug delivery using an atomic force microscopy tip-based nanoinjector, modulation of antibody/antigen interaction and enzyme activity, and blocking of ion channels.},

keywords = {Antibodies, Antigens, Atomic Force, Biosensing Techniques, carbon, Drug Delivery Systems, enzymes, Glycoproteins, I2CT, Ion Channels, Microscopy, Nanotubes, RNA, Small Interfering, Team-Bianco},

pubstate = {published},

tppubtype = {article}

}

@article{romani_targeting_2010,

title = {Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy},

author = {Nikolaus Romani and Martin Thurnher and Juliana Idoyaga and Ralph M Steinman and Vincent Flacher},

doi = {10.1038/icb.2010.39},

issn = {1440-1711},

year  = {2010},

date = {2010-01-01},

journal = {Immunology and Cell Biology},

volume = {88},

number = {4},

pages = {424--430},

abstract = {Vaccinations in medicine are commonly administered through the skin. Therefore, the vaccine is immunologically processed by antigen-presenting cells of the skin. There is recent evidence that the clinically less often used intradermal route is effective; in cases even superior to the conventional subcutaneous or intramuscular route. Professional antigen-presenting cells of the skin comprise epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(-) and dermal langerin(+) dendritic cells (DCs). In human skin, langerin(-) dermal DCs can be further subdivided on the basis of their reciprocal CD1a and CD14 expression. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Langerhans cells in human skin seem to be specialized for induction of cytotoxic T lymphocytes. Likewise, mouse Langerhans cells are capable of cross-presentation and of protecting against experimental tumours. It is desirable to harness these properties for immunotherapy. A promising strategy to dramatically improve the outcome of vaccinations is 'antigen targeting'. Thereby, the vaccine is delivered directly and selectively to defined types of skin DCs. Targeting is achieved by means of coupling antigen to antibodies that recognize cell surface receptors on DCs. This approach is being widely explored. Little is known, however, about the events that take place in the skin and the DCs subsets involved therein. This topic will be discussed in this article.},

keywords = {Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, C-Type, CD, CD14, CD1a, CROSS-PRESENTATION, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, Immunity, Immunotherapy, INDUCTION, Intradermal, Langerhans Cells, Lectins, Lymphocytes, Mannose-Binding Lectins, mouse, Receptor, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines},

pubstate = {published},

tppubtype = {article}

}

@article{flacher_targeting_2009,

title = {Targeting of epidermal Langerhans cells with antigenic proteins: attempts to harness their properties for immunotherapy},

author = {Vincent Flacher and Florian Sparber and Christoph H Tripp and Nikolaus Romani and Patrizia Stoitzner},

doi = {10.1007/s00262-008-0563-9},

issn = {1432-0851},

year  = {2009},

date = {2009-07-01},

journal = {Cancer immunology, immunotherapy: CII},

volume = {58},

number = {7},

pages = {1137--1147},

abstract = {Langerhans cells, a subset of skin dendritic cells in the epidermis, survey peripheral tissue for invading pathogens. In recent functional studies it was proven that Langerhans cells can present exogenous antigen not merely on major histocompatibility complexes (MHC)-class II molecules to CD4+ T cells, but also on MHC-class I molecules to CD8+ T cells. Immune responses against topically applied antigen could be measured in skin-draining lymph nodes. Skin barrier disruption or co-application of adjuvants was required for maximal induction of T cell responses. Cytotoxic T cells induced by topically applied antigen inhibited tumor growth in vivo, thus underlining the potential of Langerhans cells for immunotherapy. Here we review recent work and report novel observations relating to the potential use of Langerhans cells for immunotherapy. We investigated the potential of epicutaneous immunization strategies in which resident skin dendritic cells are loaded with tumor antigen in situ. This contrasts with current clinical approaches, where dendritic cells generated from progenitors in blood are loaded with tumor antigen ex vivo before injection into cancer patients. In the current study, we applied either fluorescently labeled protein antigen or targeting antibodies against DEC-205/CD205 and langerin/CD207 topically onto barrier-disrupted skin and examined antigen capture and transport by Langerhans cells. Protein antigen could be detected in Langerhans cells in situ, and they were the main skin dendritic cell subset transporting antigen during emigration from skin explants. Potent in vivo proliferative responses of CD4+ and CD8+ T cells were measured after epicutaneous immunization with low amounts of protein antigen. Targeting antibodies were mainly transported by langerin+ migratory dendritic cells of which the majority represented migratory Langerhans cells and a smaller subset the new langerin+ dermal dendritic cell population located in the upper dermis. The preferential capture of topically applied antigen by Langerhans cells and their ability to induce potent CD4+ and CD8+ T cell responses emphasizes their potential for epicutaneous immunization strategies.},

keywords = {Active, Animals, Antibodies, antibody, Antigen, Antigens, BLOOD, C-Type, cancer, CD, CD4-Positive T-Lymphocytes, CD4+ T cells, CD8-Positive T-Lymphocytes, CD8+ T cells, Dendritic Cells, DERMATOLOGY, DERMIS, Epidermis, Growth, Human, Humans, immune response, IMMUNE-RESPONSES, Immunization, Immunology, Immunotherapy, in situ, In vivo, Inbred BALB C, Inbred C57BL, INDUCTION, Langerhans Cells, LECTIN, Lectins, LYMPH, LYMPH NODE, Lymph Nodes, Major Histocompatibility Complex, Mannose-Binding Lectins, metabolism, methods, MHC class I, MHC class I molecules, Mice, Neoplasm, Neoplasms, OVALBUMIN, Patients, PROGENITORS, Protein, Proteins, RESPONSES, review, Skin, T CELLS, T-CELLS, Team-Mueller, therapy, tumor},

pubstate = {published},

tppubtype = {article}

}