022 Using single-cell transcriptomics to characterise early mechanisms of disease remission in psoriasis

Abstract

Biologic drugs have revolutionised outcomes in psoriasis, with a growing number of patients achieving clear skin (‘remission’). However, treatment involves expensive regular injections, and the long-term impact remains uncertain. An improved understanding of the early mechanisms underpinning biologics-induced remission may help inform strategies around drug withdrawal. This promises to overcome the burden of long-term continuous therapy. Here, we performed single-cell RNA sequencing on skin biopsies from 5 individuals with psoriasis who achieved remission upon treatment with the exemplar IL23p19 inhibitor risankizumab. We profiled whole skin at baseline, day-3, and -14 of treatment. Data was filtered, integrated, scaled, and normalized with the Seurat package, yielding a final dataset of 176,967 cells. A graph-based clustering approach identified 39 cell types, including keratinocyte, fibroblast, myeloid, and T cell subsets. Differential expression analysis demonstrated marked differences in transcript levels between day 0 and day 3, with the largest number of modulated genes observed among fibroblast and myeloid populations. Changes in the relative abundance of cell types became apparent at day 14, and could be verified by deconvolution of published bulk-RNA sequencing data. Finally, trajectory analysis suggested that the inflammatory cell states that characterise lesional skin are reversed soon after risankizumab treatment. Our high-resolution atlas indicates that myeloid and fibroblast populations are ‘early responders’ to risankizumab therapy, potentially driving biologic-induced remission.