Background Psoriasis is a chronic inflammatory skin disease characterised by disrupted crosstalk between keratinocytes and immune cells, resulting in epidermal dysfunction.Long non-coding RNAs (lncRNAs) regulate gene expression in a cell-or tissue-specific manner, yet their role in psoriatic epidermal dysfunction remains poorly understood.Objectives To generate a single-cell atlas of lncRNA expression in healthy and psoriatic epidermis and identify cell state-specific lncRNAs associated with disease.Methods Data from Smart-seq2 single-cell RNA sequencing of sorted CD45 and CD45 epidermal cells from healthy controls and lesional/non-lesional psoriatic skin were analysed.Selected lncRNAs were validated by RT-qPCR, single-molecule in situ hybridisation (RNAscope), and immunofluorescence.The regulation of LINC01137 was studied in IL-17A-treated primary keratinocytes and 3D epidermal models, and its function assessed using siRNA-mediated knockdown in keratinocytes. ResultsWe identified 1412 epidermal lncRNAs with robust expression across distinct keratinocyte and immune cell states.LncRNAs exhibited strong cell type-specific expression in both keratinocytes and immune cells, moreover, several lncRNAs showed selective expression in psoriasis-associated cell states.LINC01137 was enriched in activated keratinocytes, induced by IL-17A and correlated with TGF- pathway activity; its knockdown in primary keratinocytes attenuated TGF--induced SERPINE1/PAI-1 expression.LINC00892 was enriched in lesional Th1, Th17 and J o u r n a l P r e -p r o o f proliferating CD8 + T cells and showed increased expression as well as co-localisation with the T cell marker CD3 in psoriasis epidermis. ConclusionsThis study identifies the single-cell non-coding transcriptomic landscape of the psoriatic epidermis and highlights distinct lncRNA signatures in keratinocytes and immune cells, suggesting their involvement in pathogenic processes in psoriasis.
Luo et al. (Sun,) studied this question.