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@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{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{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{kwan_dendritic_2005,

title = {Dendritic cell precursors are permissive to dengue virus and human immunodeficiency virus infection},

author = {Wing-Hong Kwan and Anna-Marija Helt and Concepción Marañón and Jean-Baptiste Barbaroux and Anne Hosmalin and Eva Harris and Wolf H Fridman and Chris G F Mueller},

doi = {10.1128/JVI.79.12.7291-7299.2005},

issn = {0022-538X},

year  = {2005},

date = {2005-06-01},

journal = {Journal of Virology},

volume = {79},

number = {12},

pages = {7291--7299},

abstract = {CD14(+) interstitial cells reside beneath the epidermis of skin and mucosal tissue and may therefore play an important role in viral infections and the shaping of an antiviral immune response. However, in contrast to dendritic cells (DC) or blood monocytes, these antigen-presenting cells (APC) have not been well studied. We have previously described long-lived CD14(+) cells generated from CD34(+) hematopoietic progenitors, which may represent model cells for interstitial CD14(+) APC. Here, we show that these cells carry DC-SIGN and differentiate into immature DC in the presence of granulocyte-macrophage colony-stimulating factor. We have compared the CD14(+) cells and the DC derived from these cells with respect to dengue virus and human immunodeficiency virus type 1 (HIV-1) infection. Both cell types are permissive to dengue virus infection, but the CD14(+) cells secrete the anti-inflammatory cytokine interleukin 10 and no tumor necrosis factor alpha. Regarding HIV, the CD14(+) cells are permissive to HIV-1, release higher p24 levels than the derived DC, and more efficiently activate HIV Pol-specific CD8(+) memory T cells. The CD14(+) DC precursors infected with either virus retain their DC differentiation potential. The results suggest that interstitial CD14(+) APC may contribute to HIV-1 and dengue virus infection and the shaping of an antiviral immune response.},

keywords = {ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, APC, BLOOD, CD8-Positive T-Lymphocytes, Cell Differentiation, Cells, COLONY-STIMULATING FACTOR, Cultured, Dendritic Cells, Dengue virus, Differentiation, Epidermis, Hematopoietic Stem Cells, HIV, HIV-1, Human, Humans, IMMATURE, immunodeficiency, infection, interleukin 10, Interleukin-10, Lipopolysaccharide Receptors, MEMORY T CELLS, monocyte, Monocytes, Necrosis, precursor, PROGENITORS, Skin, T CELLS, Team-Mueller, tumor, Tumor Necrosis Factor, viral Infection, virus},

pubstate = {published},

tppubtype = {article}

}