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

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