The Keratinocyte Transcriptome in Psoriasis: Pathways Related to Immune Responses, Cell Cycle and Keratinization
Lorenzo Pasquali, Ankit Srivastava, Florian Meisgen, Kunal Das Mahapatra, Ping Xia, Ning Xu Landén, Andor Pivarcsi, Enikö Sonkoly
Psoriasis is a common immune-mediated disease resulting from altered cross-talk between keratinocytes and immune cells. Previous transcriptomic studies have identified thousands of deregulated genes in psoriasis skin; however, the transcriptomic changes confined to the epidermal compartment remained poorly characterized. The aim of this study was to characterize the transcriptomic landscape of psoriatic keratinocytes, using sorted CD45neg epidermal cells. Genes with functions in innate immunity, type I interferon response, cell cycle and keratinization were enriched among deregulated genes in psoriatic keratinocytes. Gene set enrichment analysis indicated the dominance of interleukin (IL)-22/IL-17A signatures in the epidermal psoriasis-signature. A set of deregulated genes overlapped with psoriasis-associated genetic regions, suggesting that genetic variations affecting gene expression in keratinocytes contribute to susceptibility to psoriasis. Several psoriasis-susceptibility genes, which were previously believed to be expressed preferentially or exclusively in immune cells, were identified as having altered expression in psoriatic keratinocytes. These results highlight the role of keratinocytes in the pathogenesis of psoriasis, and indicate that both genetic factors and an inflammatory microenvironment contribute to epidermal alterations in psoriasis.
Psoriasis is a common inflammatory skin disease resulting from an interplay of skin cells (keratinocytes) and immune cells. While more than 1,000 genes have altered expression in psoriasis skin, the contribution of keratinocytes to these changes is poorly characterized. This study found that keratinocytes from psoriasis skin display marked changes in gene expression, associated with proliferation, differentiation and genes induced by inflammatory mediators. Part of the identified genes overlap with genetic regions associated with susceptibility to psoriasis. These results suggest that keratinocytes in psoriasis have both intrinsic (genetic) and extrinsic (inflammation-induced) changes, and highlight the role of keratinocytes in psoriasis.