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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Epidermis / ultrastructure
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Immunohistochemistry
  • Inflammasomes / genetics*
  • Inflammasomes / metabolism
  • Keratinocytes / metabolism
  • Male
  • Microscopy, Confocal
  • Microscopy, Immunoelectron
  • Middle Aged
  • NLR Proteins / genetics*
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Psoriasis / genetics*
  • Psoriasis / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Skin / metabolism
  • Skin / pathology
  • Skin / ultrastructure
  • Young Adult

Substances

  • CARD Signaling Adaptor Proteins
  • CARD6 protein, human
  • Cytoskeletal Proteins
  • Inflammasomes
  • NLR Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Nuclear Proteins
  • PYCARD protein, human
  • Phosphoproteins
  • RNA, Messenger
  • IFI16 protein, human