ArrayExpress Uploader0humanIL22RHE3IL17RHE3IFNgRHE3CRHE3IL22RHE2IL17RHE2IFNgRHE2CRHE2IL22RHE1IL17RHE1IFNgRHE1CRHE12116arrayexpress_sid4Background: IL-17 is the defining cytokine of the Th17, Tc17, and γδ T cell populations that plays a critical role in mediating...E-GEOD-52361/profile/8773/arrayexpressuploader212cellcytokinediseaseepidermiskcspsoriasisskinskin diseaseDec.12, 2014Falseil-17-induces-an-expanded-range-of-downstream-geneE-GEOD-52361_A-AFFY-44IL-17 induces an expanded range of downstream genes in reconstituted human epidermis modelJul.11, 2014Background: 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 CEBPβ, the transcription factor regulating IL-17-responsive genes, is expressed in differentiated KCs. 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. RHE samples were treated with IFNg, IL-22 and IL-17 and compared with controlhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-52361http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-52361/samples/