title: Nickel allergies: paying the Toll for innate immunity.
abstract: Allergic contact hypersensitivity responses to the transition metal nickel (Ni(2+)) affect millions of people worldwide despite extensive legislatory efforts to ban the use of Ni(2+) in products coming into direct contact with the skin. Like other contact allergens, Ni(2+) triggers a T lymphocyte-driven delayed-type hypersensitivity reaction that is characterized by leukocyte infiltration at sites of allergen exposure. The last years have revealed that besides a hapten-specific T cell response, Ni(2+) can also directly trigger an innate immune response in resident skin cells that is necessary for mounting an allergic hypersensitivity reaction to Ni(2+). Recently, the receptor for the bacterial membrane component lipopolysaccharide, Toll-like receptor 4, has been identified as the crucial mediator of the innate immune response to Ni(2+), demonstrating that Ni(2+) employs signaling components of the bacterial defense system to elicit its allergic reactions. Here, we provide an overview of Ni(2+)-induced signaling events that have been implicated in contributing to the hypersensitivity response to this transition metal. We briefly review the causes and genetic predisposition fostering allergic responses to Ni(2+) and discuss potential therapeutic and prophylactic strategies and chances evolving from the novel insights into the molecular basis of this disease.
authors.affiliation: Department of Dermatology, Justus-Liebig-University Giessen, Gaffkystr. 14, 35392, Giessen, Germany. marc.schmidt@derma.med.uni-giessen.de
authors.forename: Marc
authors.initials: M
authors.lastname: Schmidt
authors.forename: Matthias
authors.initials: M
authors.lastname: Goebeler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003877:Dermatitis, Contact / Q000150:complications / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000150:complications / Q000276:immunology; D008969:Molecular Sequence Data; D009532:Nickel / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000737:chemistry / Q000276:immunology*
chemical_list: D051193:Toll-Like Receptors; D009532:Nickel