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Published on: October 20, 2023
Functionality and specificity of gene markers for skin sensitization in dendritic cells
Nathalie Lambrechts1, Inge Nelissen, Viggo Van Tendeloo
1Flemish Institute for Technological Research (VITO N.V.), Environmental Risk and Health Unit, Toxicology, Belgium. nathalie.lambrechts@vito.be
Toxicology Letters
|March 3, 2011
Summary
VITOSENS® gene markers show specific responses in dendritic cells (DC) activated by skin sensitizers. This research clarifies the role of these markers in DC maturation and activation by sensitizing chemicals.
Area of Science:
- Immunology
- Toxicology
- Molecular Biology
Background:
- Transcriptomic analysis identified gene expression profiles distinguishing skin sensitizers from non-sensitizers in dendritic cells (DC).
- A preliminary classification model, VITOSENS®, was developed based on these differentially expressed genes to predict chemical sensitization potential.
Purpose of the Study:
- To elucidate the functional role of VITOSENS® markers during DC maturation.
- To investigate the differential activation of VITOSENS® markers by a skin sensitizer versus a non-sensitizing danger molecule.
Main Methods:
- Pharmacological counteraction of dinitrofluorobenzene (DNFB)-induced responses in DC to assess functional relevance of VITOSENS® biomarkers.
- Flow cytometry analysis of CD86 and HLA-DR expression following COX2 inhibition and CCR2 stimulation.
- Comparison of DC gene expression (CREM, CCR2) upon exposure to DNFB versus lipopolysaccharide S (LPS).
Main Results:
- CD86 expression was downregulated by COX2 inhibition, and HLA-DR expression was reduced by CCR2 stimulation.
- The VITOSENS® genes CREM and CCR2 showed altered expression with DNFB but not with LPS.
- These findings suggest specific involvement of VITOSENS® genes in sensitizer-induced DC activation.
Conclusions:
- A subset of VITOSENS® genes are functionally implicated in sensitizer-induced DC activation.
- VITOSENS® gene markers CREM and CCR2 exhibit distinct responses to sensitizers compared to non-sensitizing danger signals, highlighting their potential specificity.
