Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis.

BACKGROUND: Nickel-induced allergic contact dermatitis (nACD) remains a major occupational skin disorder, significantly impacting the quality of life of suffering patients. Complex cellular compositional changes and associated immunological pathways are partly resolved in humans; thus, the impact of nACD on human skin needs to be further elucidated. METHODS: To decipher involved immunological players and pathways, human skin biopsies were taken at 0, 2, 48, and 96 hours after nickel patch test in six nickel-allergic patients. Gene expression profiles were analyzed via microarray. RESULTS: Leukocyte deconvolution of nACD-affected skin identified major leukocyte compositional changes at 48 and 96 hours, including natural killer (NK) cells, macrophage polarization, and T-cell immunity. Gene set enrichment analysis mirrored cellular-linked functional pathways enriched over time. NK cell infiltration and cytotoxic pathways were uniquely found in nACD-affected skin compared to sodium lauryl sulfate-induced irritant skin reactions. CONCLUSION: These results highlight key immunological leukocyte subsets as well as associated pathways in nACD, providing insights into pathophysiology with the potential to unravel novel therapeutic targets.