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Human keratinocytes stimulated with IL-17C

ABSTRACT: IL-17C is important for the pathogenesis of inflammatory diseases such as IBD and psoriasis. We found that IL-17C is highly induced in a murine model of psoriasis. Recent results suggest that IL-17C can target epithelial cells that express both IL-17RA and IL-17RE receptor chains. Here we identify genes induced in response to IL-17C treatment of human keratinocytes to provide the tools for dissection of the IL-17C signaling pathway. Human keratinocytes, HEKn, were incubated in the absence (n = 3) and presence (n = 5) of 500 ng/ml recombinant human IL-17C for 3 and 24 hours. Whole RNA was isolated via RNeasy kit (Qiagen).

ORGANISM(S): Homo sapiens

SUBMITTER: Alex Abbas

PROVIDER: E-GEOD-32620 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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IL-17A plays a central role in the expression of psoriasis signature genes through induction of IkappaB-zeta in keratinocytes

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Induction of alternative proinflammatory cytokines accounts for sustained psoriasiform skin inflammation in IL-17C+IL-6KO mice [RNA-Seq]

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IL-17A plays a central role in the expression of psoriasis signature genes through induction of IkappaB-zeta in keratinocytes

2016-03-08 | GSE77719 | GEO

Homo sapiens

Project description:Human keratinocytes stimulated with IL-17C

| PRJNA147141 | ENA

Interleukin-17A suppresses granular layer formation in a three-dimensional human epidermis model via regulation of terminal differentiation genes

Project description:Immunotherapies targeting IL-17 greatly improve plaque psoriasis. Most previous studies on IL-17 focused on the Th17 immune response, but investigation of the effects of IL-17A on psoriatic epidermal structure are limited. Using an in vitro three-dimensional (3D) human epidermis model, we investigated the effects of IL-17A and IL-17C on morphological changes and gene expression. IL-17A directly suppressed the formation of the granular layer, whereas IL-17C did not. IL-17A significantly downregulated the gene expression of profilaggrin (FLG), which is a major component of keratohyalin granules in the granular layer. Global gene expression analysis of this 3D epidermis model showed that both IL-17A and IL-17C upregulated S100A7A and type 1 interferon-related genes including MX1, IFI44L, XAF1 and IFIT1. However, only IL-17A directly downregulated keratinocyte differentiation-related and cornified envelope-related genes including FLG, LOR, C1ORF68, LCE1E, LCE1B, KRT10, CST6 and RPTN. In conclusion, IL-17A, a systemic inflammatory cytokine, affected keratinization in our 3D epidermis model. In contrast, IL-17C, a locally produced cytokine, did not have strong effects on keratinization. Targeting IL-17A does not only reduce inflammation but it may also directly affect epidermal differentiation in psoriasis.

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