title: NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis.
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.
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: Mari H
authors.initials: MH
authors.lastname: Tervaniemi
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.|Science for Life Laboratory, Solna, Sweden.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Tiina
authors.initials: T
authors.lastname: Skoog
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: H Annika
authors.initials: HA
authors.lastname: Siitonen
authors.affiliation: Helsinki Burn Center, Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Vuola
authors.affiliation: Department of Pharmacology, Medicum, University of Helsinki, Helsinki, Finland.
authors.forename: Kristo
authors.initials: K
authors.lastname: Nuutila
authors.affiliation: Biocenter Oulu, Department of Pathology, University of Oulu, Oulu, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Johnsson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Linnarsson
authors.affiliation: Department of Dermatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Suomela
authors.affiliation: Department of Pharmacology, Medicum, University of Helsinki, Helsinki, Finland.
authors.forename: Esko
authors.initials: E
authors.lastname: Kankuri
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.|Science for Life Laboratory, Solna, Sweden.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Elomaa
mesh_terms: D000368:Aged; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D000070576:NLR Proteins / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D055815:Young Adult
chemical_list: D053468:CARD Signaling Adaptor Proteins; C478017:CARD6 protein, human; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D000070576:NLR Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D009687:Nuclear Proteins; C402202:PYCARD protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; C076700:IFI16 protein, human