Figure 1.

Schematic mechanism of metal ion–induced allergic contact dermatitis. (a) Sensitization phase in metal allergy. Step 1: Metal ions form complexes with partner molecules within the body, thereby becoming antigens. A hapten (metal ion) combines with a native protein and activates keratinocytes (KCs), cutaneous Langerhans cells (LCs), and dermal dendritic cells (DCs) through the innate immune system; Step 2: Activated DCs capture antigens, mature, and migrate to the regional lymph nodes via afferent lymphatics; Step 3: Migrated DCs present antigens to naive T cells in draining lymph nodes. NK T cells affect DC functions and regulate the excessive immune response; (b) Elicitation phase in metal allergy. Step 1: KCs are activated by re-exposure to haptens and produce various cytokines and chemokines that activate endothelial cells and draining memory metal-specific T cells; Step 2: Infiltrated metal-specific effector T cells are activated and produce proinflammatory cytokines and chemokines that activate KCs and induce further inflammatory cell infiltration; Step 3: NK T cells may regulate the excessive acquired immune response caused by metal-specific effector T cells.