Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model

Nickel is one of the most common contact allergens worldwide. Despite this prevalence, many of the underlying immunological mechanisms responsible for nickel allergy remain unclear. This knowledge gap is partially attributable to the inherent resistance of laboratory rodents (mice and rats) to dermal sensitization with nickel salts. The fundamental goal of this study was to assess the potential utility of the novel humanized Toll-like receptor-4 (hTLR-4) mouse model for use in future in vivo studies of nickel allergy. Accordingly, hTLR-4 positive and negative mice of both sexes were first incorporated into a Local Lymph Node Assay (LLNA) to evaluate dermal sensitization following topical exposure to soluble nickel salts (NiSO4). The ensuing immune responses were then characterized further by incorporating female and male hTLR-4 positive mice into a non-radioactive endpoint-based assay. Utilizing the same exposure scheme as in the LLNA, mice were euthanized following exposure and the auricular lymph nodes, spleen, and blood were collected to assess various immunological parameters associated with allergy and ACD.