title: 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®) 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® 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® 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® genes may be functionally involved in sensitizer-induced DC activation. By comparing their responsiveness towards a non-sensitizing danger signal and a sensitizer, VITOSENS® gene markers CREM and CCR2 appear to display a specific response.
authors.affiliation: Flemish Institute for Technological Research (VITO N.V.), Environmental Risk and Health Unit, Toxicology, Belgium. nathalie.lambrechts@vito.be
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lambrechts
authors.forename: Inge
authors.initials: I
authors.lastname: Nelissen
authors.forename: Viggo
authors.initials: V
authors.lastname: Van Tendeloo
authors.forename: Hilda
authors.initials: H
authors.lastname: Witters
authors.forename: Rosette
authors.initials: R
authors.lastname: Van Den Heuvel
authors.forename: Jef
authors.initials: J
authors.lastname: Hooyberghs
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
mesh_terms: D000826:Animal Testing Alternatives; D018952:Antigens, CD34 / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000235:genetics* / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D012313:RNA / Q000737:chemistry / Q000235:genetics; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018952:Antigens, CD34; C515334:CCR2 protein, human; D054390:Receptors, CCR2; D012313:RNA; D004139:Dinitrofluorobenzene; D051546:Cyclooxygenase 2