Type I interferon: Potential therapeutic target for psoriasis?

Yihong Yao, Laura Richman, Chris Morehouse, Melissa de los Reyes, Brandon W. Higgs, Anmarie Boutrin, Barbara White, Anthony Coyle, James Krueger, Peter A. Kiener, Bahija Jallal

Research output: Contribution to journalArticlepeer-review

202 Scopus citations


Background: Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. To better understand the pathogenesis of this disease and identify potential mediators, we used whole genome array analysis to profile paired lesional and nonlesional psoriatic skin and skin from healthy donors. Methodology/Principal Findings: We observed robust overexpression of type I interferon (IFN)-inducible genes and genomic signatures that indicate T cell and dendritic cell infiltration in lesional skin. Up-regulation of mRNAs for IFN-α subtypes was observed in lesional skin compared with nonlesional skin. Enrichment of mature dendritic cells and 2 type I IFN-inducible proteins, STAT1 and ISG15, were observed in the majority of lesional skin biopsies. Concordant overexpression of IFN-γ and TNF-α-inducible gene signatures occurred at the same disease sites. Conclusions/Significance: Up-regulation of TNF-α and elevation of the TNF-α-inducible gene signature in lesional skin underscore the importance of this cytokine in psoriasis; these data describe a molecular basis for the therapeutic activity of anti-TNF-α agents. Furthermore, these findings implicate type I IFNs in the pathogenesis of psoriasis. Consistent and significant up-regulation of type I IFNs and their associated gene signatures in psoriatic skin suggest that type I IFNs may be potential therapeutic targets in psoriasis treatment.

Original languageEnglish (US)
Article numbere2737
JournalPLoS One
Issue number7
StatePublished - Jul 16 2008
Externally publishedYes

ASJC Scopus subject areas

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


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