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

Area of Science:

• Immunology
• Dermatology
• Allergy Research

Background:

• Metal allergies are delayed-type hypersensitivity reactions involving sensitization and elicitation phases.
• Mechanisms include Toll-like receptor 4 and NLRP3 inflammasome activation, but responsible cells are unknown.
• The role of circulating versus tissue-resident T cells in elicitation is unclear.

Purpose of the Study:

• To investigate the cell types involved in human nickel hypersensitivity.
• To differentiate between early and late phase responses in nickel allergy.
• To understand the contribution of T cells in metal hypersensitivity.

Main Methods:

• Single-cell RNA sequencing and immunofluorescence analysis of human skin samples.
• Nickel-sensitized donors were exposed epicutaneously to nickel or diluent.
• Skin samples were analyzed at 8 and 72 hours post-exposure.

Main Results:

• Nickel activated specific endothelial cells, keratinocytes, fibroblasts, and dendritic cells within 8 hours.
• These cells co-expressed DCN and CCL21, interacting with Toll-like receptor 4.
• Skin-resident T cells showed no early gene expression changes; however, KLF2+ central memory T cells infiltrated after 72 hours.

Conclusions:

• Early nickel hypersensitivity involves activation of non-T cells, including endothelial cells and keratinocytes.
• Tissue-resident T cells are not involved in the initial response.
• Late-phase response is characterized by the infiltration of circulating KLF2+ central memory T cells, similar to budesonide allergy.