Single Cell Analysis Reveals Dynamic Changes of Distinct Cell Populations in Human Nickel Allergy.

backgroundMetal allergies are prime examples of delayed-type hypersensitivity divided into two phases: in the sensitization phase, initial contact with an allergen leads to activation of skin-resident cells and formation of metal-reactive T cells. during elicitation, these T cells mount an immune response resulting in clinically apparent eczema within 72 h after exposure. Two main mechanisms have been implicated in the initiation of metal hypersensitivity: direct or indirect activation of innate immune receptors such as Toll-like receptor 4, and conditional innate immune activation via the NLRP3 inflammasome. Yet, the responsible cell type(s) mediating these responses are unknown. Moreover, it is unclear whether the elicitation phase is mainly dominated by infiltration of circulating metal-responsive T cells or if tissue-resident T cells contribute.

methodsHere, we analyzed the relevance of different cell types in human nickel hypersensitivity by single-cell RNA sequencing and immunofluorescence analysis of skin samples of nickel-sensitized donors epicutaneously exposed to diluent and nickel for 8 or 72 h. RESULTS AND

conclusionNickel specifically activated distinct populations of endothelial cells, suprabasal keratinocytes, fibroblasts, and CCR7