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Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel

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Fejer,  György
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Tchaptchet,  Sandrine
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Keck,  Simone
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Kalis,  Christoph
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Nielsen,  Peter J.
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Galanos,  Chris
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Freudenberg,  Marina A.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Schmidt, M., Raghavan, B., Müller, V., Vogl, T., Fejer, G., Tchaptchet, S., et al. (2010). Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nature Immunology, 11, 814-819.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-8EDA-0
Abstract
Allergies to nickel (Ni2+) are the most frequent cause of contact hypersensitivity (CHS) in industrialized countries. The efficient development of CHS requires both a T lymphocyte-specific signal and a proinflammatory signal. Here we show that Ni2+ triggered an inflammatory response by directly activating human Toll-like receptor 4 (TLR4). Ni2+-induced TLR4 activation was species-specific, as mouse TLR4 could not generate this response. Studies with mutant TLR4 proteins revealed that the non-conserved histidines 456 and 458 of human TLR4 are required for activation by Ni2+ but not by the natural ligand lipopolysaccharide. Accordingly, transgenic expression of human TLR4 in TLR4-deficient mice allowed efficient sensitization to Ni2+ and elicitation of CHS. Our data implicate site-specific human TLR4 inhibition as a potential strategy for therapeutic intervention in CHS that would not affect vital immune responses.