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. 2010 Sep;11(9):814-9.
doi: 10.1038/ni.1919. Epub 2010 Aug 15.

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

Marc Schmidt  1 , Badrinarayanan Raghavan, Verena Müller, Thomas Vogl, György Fejer, Sandrine Tchaptchet, Simone Keck, Christoph Kalis, Peter J Nielsen, Chris Galanos, Johannes Roth, Arne Skerra, Stefan F Martin, Marina A Freudenberg, Matthias Goebeler
Affiliations

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

Marc Schmidt et al. Nat Immunol. 2010 Sep.

Abstract

Allergies to nickel (Ni(2+)) 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 Ni(2+) triggered an inflammatory response by directly activating human Toll-like receptor 4 (TLR4). Ni(2+)-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 Ni(2+) but not by the natural ligand lipopolysaccharide. Accordingly, transgenic expression of human TLR4 in TLR4-deficient mice allowed efficient sensitization to Ni(2+) 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.

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Comment in

  • How nickel turns on innate immune cells.
    Roediger B, Weninger W. Roediger B, et al. Immunol Cell Biol. 2011 Jan;89(1):1-2. doi: 10.1038/icb.2010.114. Epub 2010 Oct 12. Immunol Cell Biol. 2011. PMID: 20938456 No abstract available.

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