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

Le résumé fourni par la source

ABSTRACT Background Metal 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. Methods Here, 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 Conclusion Nickel specifically activated distinct populations of endothelial cells, suprabasal keratinocytes , fibroblasts, and CCR7 + dendritic cells, co‐expressing the TLR4 ‐interacting proteogylcan DCN and CCR7 ligand CCL21 within 8 h. Skin‐resident T cells were not involved in the early hypersensitivity response, as their gene expression remained unaltered 8 h after nickel exposure. However, substantial changes in the cutaneous T cell compartments occurred after 72 h, with massive infiltration of KLF2 + central memory T cells being a recurrent feature of both nickel‐sensitized patients and individuals allergic to the glucocorticoid contact allergen budesonide.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.