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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE142552 | GEO | 2020/12/31

REPOSITORIES: GEO

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