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      Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects : Current knowledge assembled at an international workshop at BfR, Germany

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          Abstract

          Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German ‘Federal Institute for Risk Assessment’ hosted an ‘International Workshop on Contact Dermatitis’. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15–20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.

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          Most cited references186

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          Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset.

          Since the discovery of T helper type 1 and type 2 effector T cell subsets 20 years ago, inducible regulatory T cells and interleukin 17 (IL-17)-producing T helper cells have been added to the 'portfolio' of helper T cells. It is unclear how many more effector T cell subsets there may be and to what degree their characteristics are fixed or flexible. Here we show that transforming growth factor-beta, a cytokine at the center of the differentiation of IL-17-producing T helper cells and inducible regulatory T cells, 'reprograms' T helper type 2 cells to lose their characteristic profile and switch to IL-9 secretion or, in combination with IL-4, drives the differentiation of 'T(H)-9' cells directly. Thus, transforming growth factor-beta constitutes a regulatory 'switch' that in combination with other cytokines can 'reprogram' effector T cell differentiation along different pathways.
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            Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells.

            Interleukin 22 (IL-22) is a cytokine produced by the T(H)-17 lineage of helper T cells and NK-22 subset of natural killer cells that acts on epithelial cells and keratinocytes and has been linked to skin homeostasis and inflammation. Here we characterize a population of human skin-homing memory CD4(+) T cells that expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but neither IL-17 nor interferon-gamma (IFN-gamma). Clones isolated from this population produced IL-22 only and had low or undetectable expression of the T(H)-17 and T helper type 1 (T(H)1) transcription factors RORgammat and T-bet. The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor-dependent way. Our findings delineate a previously unknown subset of human CD4(+) effector T cells dedicated to skin pathophysiology.
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              Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases.

              Caspases not only play an essential role during apoptotic cell death, but a subfamily of them-the inflammatory caspases-are associated with immune responses to microbial pathogens. Activation of inflammatory caspases, such as caspase-1 and caspase-5, occurs upon assembly of an intracellular complex, designated the inflammasome. This results in the cleavage and activation of the proinflammatory cytokines IL-1beta and IL-18. Mutations in one of the scaffold proteins of the inflammasome, NALP3/Cryopyrin, are associated with autoinflammatory disorders underscoring the importance of regulating inflammatory caspase activation.
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                Author and article information

                Contributors
                +49-30-184123842 , ++49-30-184124928 , Tewes.Tralau@bfr.bund.de
                +49-30-184124538 , ++49-30-184124928 , Andreas.Luch@bfr.bund.de
                Journal
                Cell Mol Life Sci
                Cellular and Molecular Life Sciences
                SP Birkhäuser Verlag Basel (Basel )
                1420-682X
                1420-9071
                14 October 2011
                14 October 2011
                March 2012
                : 69
                : 5
                : 763-781
                Affiliations
                [1 ]Department of Product Safety, German Federal Institute for Risk Assessment (BfR), Thielallee 88-92, 14195 Berlin, Germany
                [2 ]Research Institute for Fragrance Materials, Hackensack, NJ USA
                [3 ]AkzoNobel N.V., Arnhem, The Netherlands
                [4 ]DABMEB Consultancy Ltd, Sharnbrook, UK
                [5 ]Nottingham University Hospitals, Nottingham, UK
                [6 ]Department of Social Medicine, Occupational and Environmental Dermatology, University of Heidelberg, Heidelberg, Germany
                [7 ]Harvard Skin Disease Research Center, Boston, MA USA
                [8 ]School of Medicine, University of Maryland, Baltimore, MD USA
                [9 ]Department of Derma-allergology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
                [10 ]Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, Gothenburg, Sweden
                [11 ]Faculty of Life Sciences, University of Manchester, Manchester, UK
                [12 ]Dermatochimie, University of Strasbourg, Strasbourg, France
                [13 ]Department of Experimental Toxicology and ZEBET, Center for Alternatives to Animal Testing, German Federal Institute for Risk Assessment (BfR), Berlin, Germany
                [14 ]Department of Dermatology, University of California San Francisco, San Francisco, CA USA
                [15 ]Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
                [16 ]Department of Dermatology and Allergology, University Hospitals Aachen, Aachen, Germany
                [17 ]VU University Medical Center, Amsterdam, The Netherlands
                [18 ]Department of Dermatology, University of Göttingen, Göttingen, Germany
                [19 ]National Institute for Public Health and the Environment, Bilthoven, The Netherlands
                [20 ]St. John’s Institute of Dermatology, St. Thomas’ Hospital, London, UK
                Article
                846
                10.1007/s00018-011-0846-8
                3276771
                21997384
                8765ec43-996d-4fe1-a937-953d57c58ab3
                © The Author(s) 2011
                History
                : 14 June 2011
                : 29 August 2011
                : 20 September 2011
                Categories
                Review
                Custom metadata
                © Springer Basel AG 2012

                Molecular biology
                molecular mechanisms,epidemiology,dermatitis,contact allergy,regulatory aspects
                Molecular biology
                molecular mechanisms, epidemiology, dermatitis, contact allergy, regulatory aspects

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