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

Schmidt, Marc; Raghavan, Badrinarayanan; Müller, Verena; Vogl, Thomas; Fejer, György; Tchaptchet, Sandrine; Keck, Simone; Kalis, Christoph; Nielsen, Peter J.; Galanos, Chris; Roth, Johannes; Skerra, Arne; Martin, Stefan; Freudenberg, Marina A.; Goebeler, Matthias

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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;

/persons/resource/persons191059

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: https://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.