IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model. Academic Article uri icon

Overview

abstract

  • BACKGROUND: IL-17 is the defining cytokine of the Th17, Tc17, and γδ T cell populations that plays a critical role in mediating inflammation and autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines with relevant contributions of IFN-γ, TNF-α, and IL-17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the other key mediators involved in the psoriasis cytokine cascade that are capable of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate the expression of a limited number of genes in monolayer keratinocytes cultured in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Given the clinical efficacy of anti-IL-17 agents is associated with an impressive reduction in a large set of inflammatory genes, we sought a full-thickness skin model that more closely resemble in vivo epidermal architecture. Using a reconstructed human epidermis (RHE), IL-17 was able to upregulate 419 gene probes and downregulate 216 gene probes. As possible explanation for the increased gene induction in the RHE model is that C/CAAT-enhancer-binding proteins (C/EBP) -β, the transcription factor regulating IL-17-responsive genes, is expressed preferentially in differentiated keratinocytes. CONCLUSIONS/SIGNIFICANCE: The genes identified in IL-17-treated RHE are likely relevant to the IL-17 effects in psoriasis, since ixekizumab (anti-IL-17A agent) strongly suppressed the "RHE" genes in psoriasis patients treated in vivo with this IL-17 antagonist.

publication date

  • February 28, 2014

Research

keywords

  • CCAAT-Enhancer-Binding Protein-beta
  • Epidermis
  • Interleukin-17
  • Keratinocytes

Identity

PubMed Central ID

  • PMC3938679

Scopus Document Identifier

  • 84896503749

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0090284

PubMed ID

  • 24587313

Additional Document Info

volume

  • 9

issue

  • 2