IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model

Andrea Chiricozzi, Kristine E. Nograles, Leanne M. Johnson-Huang, Judilyn Fuentes-Duculan, Irma Cardinale, Kathleen M. Bonifacio, Nicholas Gulati, Hiroshi Mitsui, Emma Guttman-Yassky, Mayte Suarez-Farinas, James G. Krueger

Risultato della ricerca: Contributo in rivistaArticolo in rivista


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/CAATenhancer- 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. © 2014 Chiricozzi et al.
Lingua originaleEnglish
pagine (da-a)e90284-N/A
RivistaPLoS One
Stato di pubblicazionePubblicato - 2014


  • IL-17
  • psoriasis


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