The gene expression and immunohistochemical time-course of diphenylcyclopropenone induced contact allergy in healthy humans following repeated epicutaneous challenges

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 challenges with DPCP 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 dataset.

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 out 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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