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Sci Rep. 2016 Mar 15;6:22745. doi: 10.1038/srep22745.

NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis.

Author information

1
Folkhälsan Institute of Genetics, Helsinki, Finland.
2
Department of Medical and Clinical Genetics, Medicum and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
3
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
4
Science for Life Laboratory, Solna, Sweden.
5
Helsinki Burn Center, Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
6
Department of Pharmacology, Medicum, University of Helsinki, Helsinki, Finland.
7
Biocenter Oulu, Department of Pathology, University of Oulu, Oulu, Finland.
8
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
9
Department of Dermatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Abstract

Psoriatic skin differs distinctly from normal skin by its thickened epidermis. Most gene expression comparisons utilize full-thickness biopsies, with substantial amount of dermis. We assayed the transcriptomes of normal, lesional, and non-lesional psoriatic epidermis, sampled as split-thickness skin grafts, with 5'-end RNA sequencing. We found that psoriatic epidermis contains more mRNA per total RNA than controls, and took this into account in the bioinformatic analysis. The approach highlighted innate immunity-related pathways in psoriasis, including NOD-like receptor (NLR) signaling and inflammasome activation. We demonstrated that the NLR signaling genes NOD2, PYCARD, CARD6, and IFI16 are upregulated in psoriatic epidermis, and strengthened these findings by protein expression. Interestingly, PYCARD, the key component of the inflammasome, showed an altered expression pattern in the lesional epidermis. The profiling of non-lesional skin highlighted PSORS4 and mitochondrially encoded transcripts, suggesting that their gene expression is altered already before the development of lesions. Our data suggest that all components needed for the active inflammasome are present in the keratinocytes of psoriatic skin. The characterization of inflammasome pathways provides further opportunities for therapy. Complementing previous transcriptome studies, our approach gives deeper insight into the gene regulation in psoriatic epidermis.

PMID:
26976200
PMCID:
PMC4792137
DOI:
10.1038/srep22745
[Indexed for MEDLINE]
Free PMC Article

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