Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis. Issue 3 (12th August 2020)

• Record Type: Journal Article
• Authors: Wisgrill, Lukas; Werner, Paulina; Jalonen, Erja; Berger, Angelika; Lauerma, Antti; Alenius, Harri; Fyhrquist, Nanna
• Is Part Of: Allergy. Volume 76:Issue 3(2021)
• Page Start: 804
• Page End: 815
• Publication Date: 2020-08-12
• Subjects: contact dermatitis -- nickel -- transcriptomics; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.14519
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: 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. Abstract : Late‐phase nickel challenge induces major changes in leukocyte composition including influx and activation of NK cells, macrophage polarization, and T‐cell immunity. MMP12 and SOCS3 are highly upregulated, linking our human findings to previous findings in mice. NK cell infiltration and cytotoxic pathways were found to be uniquely upregulated in nickel‐induced allergic skin responses compared to SLS‐induced irritant skin responses. Abbreviations: MMP12, matrix metallopeptidase 12; NiSO4, nickel sulfate; SLS, sodium lauryl sulfate; SOCS3, suppressor of cytokine signaling 3.