The gene expression and immunohistochemical time‐course of diphenylcyclopropenone‐induced contact allergy in healthy humans following repeated epicutaneous challenges |
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| Authors: | Kristian F. Mose Mark Burton Mads Thomassen Flemming Andersen Torben A. Kruse Qihua Tan Lone Skov Mads A. Røpke Thomas Litman Ole Clemmensen Bjarne W. Kristensen Peter S. Friedmann Klaus E. Andersen |
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| Affiliation: | 1. Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, Odense C, Denmark;2. Dermatological Investigations Scandinavia, Odense University Hospital, University of Southern Denmark, Odense C, Denmark;3. Department of Clinical Genetics, Odense University Hospital, University of Southern Denmark, Odense C, Denmark;4. Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C, Denmark;5. Department of Dermato‐Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark;6. Departments of Clinical Pharmacology and Molecular Biomedicine, LEO Pharma A/S, Ballerup, Denmark;7. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen N, Denmark;8. Department of Clinical Pathology, Odense University Hospital, University of Southern Denmark, Odense C, Denmark;9. Division of Infection, Inflammation & Immunity, Sir Henry Wellcome Laboratories, Southampton University Hospitals NHS Trust, Southampton, UK;10. Centre for Innovative Medical Technology, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark |
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| Abstract: | The gene expression time‐course of repeated challenge of contact allergy (CA) remains largely unknown. Therefore, using diphenylcyclopropenone (DPCP) as model allergen in healthy humans we set out to examine: (i) the monotonous and complex gene expression time‐course trajectories following repeated DPCP challenges to find the predominant gene expression pattern, (ii) the time‐course of cell infiltration following repeated DPCP challenges and (iii) the transcriptome of a repeated CA exposure model. We obtained punch biopsies from control and DPCP‐exposed skin from ten DPCP sensitized individuals at 5‐6 monthly elicitation challenges. Biopsies were used for microarray gene expression profiling, histopathology and immunohistochemical staining. Validation of microarray data by qRT‐PCR was performed on 15 selected genes. Early gene expression time points were also validated in an independent data set. An increasing and decreasing trend in gene expression followed by a plateau was predominantly observed during repeated DPCP challenges. Immune responses reached a plateau after two challenges histopathologically, immunohistochemically and in the time‐course gene expression analysis. Transcriptional responses over time revealed a Th1/Th17 polarization as three upstream regulators (IFN‐γ, IL‐1 and IL‐17) activated most of the top upregulated genes. Of the latter genes, 9 of 10 were the same throughout the time course. Excellent correlations between array and PCR data were observed. The transcriptional responses to DPCP over time followed a monotonous pattern. This response pattern confirms and supports the newly reported clinical time‐course observations in de novo‐sensitized individuals showing a plateau response, and thus, there is concordance between clinical response, histopathology, immunohistochemistry and microarray gene expression in volunteers de novo‐sensitized to DPCP. |
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| Keywords: | de novo sensitization microarray rechallenge time‐course analysis transcriptional profiling |
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