Functionality and specificity of gene markers for skin sensitization in dendritic cells

Abstract

Transcriptomic analyses revealed a discriminating gene expression profile in human CD34(+) progenitor-derived dendritic cells (DC) after exposure to skin sensitizers versus non-sensitizers. Starting from the differential expression in a small set of genes, a preliminary classification model (VITOSENS (R)) has been developed to identify chemicals as (non-)sensitizing. The objective of the current study is to gain knowledge on the role of the VITOSENS (R) markers in the DC maturation process, as well as to investigate their activation by a skin sensitizer versus a non-sensitizing danger molecule. To evaluate the functional relevance of VITOSENS (R) biomarkers in DC maturation, their response induced by the sensitizer dinitrofluorobenzene (DNFB) was pharmacologically counteracted. Flow cytometry analyses revealed that CD86 was down-regulated after COX2 inhibition, whereas expression of HLA-DR was reduced by stimulating CCR2. When exposing DC to DNFB versus lipopolysaccharide S (LPS), expression of most discriminating genes CREM and CCR2 was not altered by LPS as opposed to DNFB. To summarize, the observations in this research indicate that a selection of the VITOSENS (R) genes may be functionally involved in sensitizer-induced DC activation. By comparing their responsiveness towards a non-sensitizing danger signal and a sensitizer, VITOSENS (R) gene markers CREM and CCR2 appear to display a specific response. (C) 2011 Elsevier Ireland Ltd. All rights reserved.