038 Single-cell sequencing of freshly isolated cells from lesional and peri-lesional skin to explore cellular origins of IL-17 isoforms in psoriasis

Psoriasis is the most common chronic inflammatory skin disease in adults, characterized by immune cell infiltration, expansion of disease-associated lymphocytes, and epidermal hyperplasia. Increasing evidence highlights central role interleukin (IL)-17A IL-17F its pathobiology. IL-17A IL-17F, known to be produced activated T helper 17 cells, can form homodimers or heterodimers drive aberrant keratinocyte biology. We applied single-cell RNA sequencing characterize infiltrate psoriatic further understand cellular sources IL-17F. Biopsies lesions peri-lesional were collected from six patients with moderate severe plaque psoriasis. Transcriptomic profiles 15,690 isolated CD45+ cells determined fresh tissue rapidly dissociated mechanical short enzymatic dissociation, lymphocyte sub-clusters manually curated based on canonical cell-type markers. IL-17+ markedly expanded compared samples, consistent a pathobiological role. Cells that separately express exist significantly more abundant than co-expressing cells. IL-17-producing predominantly CD4+ CD8+ expressing skin-resident -homing markers, but not limited these types. IL-17F+ subset had similar transcriptional signatures IL-17A+ supporting addition as key proinflammatory cytokine Our data suggest that, fully ameliorate IL-17 signaling, both isoforms must neutralized, clinical findings phase 3b BE RADIANT study psoriasis patients, which bimekizumab was superior secukinumab.