POS0450 TEMPORAL MIGRATION OF IMMUNE CELLS FROM PSORIATIC SKIN TO JOINTS INITIATING SYNOVIAL INFLAMMATION IN PSORIATIC ARTHRITIS

BackgroundSpreading of inflammation from skin to joint is a key question behind the pathogenesis of psoriatic arthritis (PsA). Psoriasis (PsO), being one of the most prevalent skin diseases, usually anticipates joint manifestations, suggesting spreading of skin to joint disease, which happens in about 30% of the patients with psoriasis.1 To date, it is still obscure why the inflammatory process in some patients with PsO remains restrained to the skin, whereas in other patients it extents to tendons and joints.ObjectivesUsing a pre-clinical model of PsA, we aimed to unveil the skin-joint axis, i.e. the spreading of psoriatic inflammation from the skin to the joints.MethodsKAEDE transgenic mice expressing a photo-convertible fluorescent reporter were used to assess cell trafficking from inflamed skin to other organs in the mouse model of IL-23 overexpression (IL-23OE) induced PsA. Psoriatic skin lesions were irradiated with UV light to trigger the photoswitch from KAEDEGREEN to KAEDERED. Migration to different organs was determined by flow cytometry. Imaging flow cytometry was used to characterize the type of cells migrating from the skin to the joints. Migrating cells were further characterized by single-cell RNA-sequencing (scRNAseq) and functional analyses.ResultsMRI imaging and histological evaluation of IL-23OE mice revealed skin inflammation preceding joint inflammation in both wild-type and KAEDE-transgenic mice. Specific leukocyte migration from the skin to the joints started shortly after the onset of skin inflammation and before onset of inflammation within the joints of KAEDE transgenic mice. No migration was observed in healthy control animals. Other organs such as spleen or lymph nodes showed no model-dependent migration. Imaging flow cytometry revealed that the cells migrating to the joints were predominantly CD45+ CD11b+ cells. ScRNAseq analysis of sorted KAEDERED cells from inflamed joints confirmed that approximately 80% of the migrating cells were macrophages. Differential gene expression and pathway analysis revealed an imbalance between pro- and anti-inflammatory macrophages in the joints of experimental psoriatic arthritis.ConclusionWe describe IL-23-mediated migration of skin-derived macrophages from the skin to the joints during the onset of experimental psoriatic arthritis. This process may explain the spreading from psoriatic skin to joint disease as these cells foster the development by local cytokine production once arrived in the joints.References[1]Veale, D.J. & Fearon, U. The pathogenesis of psoriatic arthritis. Lancet391, 2273-2284 (2018).Disclosure of InterestsNone declared.