Genome Wide Transcriptome Analysis of Dendritic Cells Identifies Genes with Altered Expression in Psoriasis

Kata Filkor, Z. Hegedűs, András Szász, Vilmos Tubak, L. Kemény, É. Kondorosi, István Nagy

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS) or peptidoglycan (PGN) induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation, proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the transcriptional diversity of primary human immature dendritic cells (iDCs) upon PGN induced tolerance. Using SAGE-Seq approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand. Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (Kegg) analysis showed marked enrichment of immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators, negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature dendritic cells with anti-TNF-α inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome sequencing of stimulated/restimulated iDCs identified numerous genes with altered expression to date not associated with role in chronic inflammation, underlying the relevance of our in vitro model for further characterization of IFN-primed iDCs.

Original languageEnglish
Article numbere73435
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 9 2013

Fingerprint

psoriasis
Gene Expression Profiling
dendritic cells
transcriptomics
Psoriasis
Dendritic Cells
Genes
Genome
Peptidoglycan
immatures
peptidoglycans
genome
inflammation
genes
Inflammation
Transcriptome
Innate Immunity
Chemical activation
Encyclopedias
Gene Ontology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Genome Wide Transcriptome Analysis of Dendritic Cells Identifies Genes with Altered Expression in Psoriasis. / Filkor, Kata; Hegedűs, Z.; Szász, András; Tubak, Vilmos; Kemény, L.; Kondorosi, É.; Nagy, István.

In: PLoS One, Vol. 8, No. 9, e73435, 09.09.2013.

Research output: Contribution to journalArticle

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