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

Title	Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel.
Authors	J. Nielsen, Marc Schmidt-Supprian, György Fejer, Thomas Vogl, C H Kalis, Matthias Goebeler, Marina Freudenberg, Chris Galanos, Varun B. Raghavan, Arne Skerra, Thomas Martin, Johannes Roth, S Keck, Verena Gauss-Müller, Sandrine Tchaptchet
Magazine	Nature Immunology
Date	08/31/2010
DOI	10.1038/ni.1919
Introduction	Nickel allergies are the leading cause of contact hypersensitivity (CHS) in industrialised regions. CHS development requires both a T lymphocyte-specific and a proinflammatory signal. This study reveals that nickel directly activates the human Toll-like receptor 4 (TLR4), inducing inflammation. Notably, this activation is species-specific, as mouse TLR4 does not respond. Mutant TLR4 protein studies indicate that human TLR4 histidines 456 and 458 are essential for nickel activation, while not affecting lipopolysaccharide responses. Transgenic mice expressing human TLR4 can be sensitised to nickel, implicating site-specific human TLR4 inhibition as a potential therapeutic strategy for CHS without impacting vital immune functions.
Quote	J. Nielsen, Marc Schmidt-Supprian and György Fejer et al. Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. 2010. DOI: 10.1038/ni.1919
Element	Nickel (Ni)
Industry	Pharmaceutical Industry