Molecular Mechanisms of Nickel Allergy

Abstract

Allergic contact hypersensitivity to metals is a delayed-type allergy. Although various metals are known to produce an allergic reaction, nickel is the most frequent cause of metal allergy. Researchers have attempted to elucidate the mechanisms of metal allergy using animal models and human patients. Here, the immunological and molecular mechanisms of metal allergy are described based on the findings of previous studies, including those that were recently published. In addition, the adsorption and excretion of various metals, in particular nickel, is discussed to further understand the pathogenesis of metal allergy.

Keywords: DC; DTH; Ni; T cell; TLR; TSLP; metal allergy.

Figure 1

A complex mechanism of metal allergy. The sensitization phase begins after nickel exposure to the skin. Nickel penetration into the skin results in the production of proinflammatory cytokines (TNF-α and IL-1β), TSLP, and chemokines, which induce activation and migration of haptenated protein-loaded epidermal and dermal DCs through afferent lymph to the draining lymph nodes. Particularly in humans, nickel directly activates the TLR4 pathway in DCs. In the draining lymph nodes, haptenated-peptide presentation results in the proliferation, activation and subsequent differentiation of hapten-specific T cells. Secretion of cytokines in the draining lymph nodes during the sensitization phase contributes to efficient hapten-specific T cell activation, proliferation, and differentiation. At the end of this phase, primed specific T cells migrate out of the lymph nodes to the skin. In the elicitation phase, the subsequent application of the same hapten leads to uptake by cells, which is presented to the recirculating hapten-specific T cells. The activated T cells produce inflammatory cytokines and chemokines at the site of exposure that promote an allergic reaction, leading to the development of characteristic skin lesions.