Single cell characterization of circulating and synovial derived immune cells reveals enrichment of CXCL16+ dendritic cells and granzyme K+ T cells in psoriatic arthritis 4728

Description Psoriatic arthritis (PsA) is an immune-mediated joint disease, often developing within 10 years of onset of psoriasis, with ∼30% of patients progressing to joint involvement. Biomarkers of disease progression are essential for improving patient outcomes, however the immunological progression of disease is not fully understood. To explore the immune landscape of PsA, we isolated immune cells from 4 matched PsA blood and synovial fluid patient samples and performed multimodal single-cell sequencing. Our analysis revealed an enrichment of CD1c+ and CD141+ dendritic cells (DCs) expressing CXCL16 in the synovial fluid. Pathway analysis of these DCs indicated enhanced antigen presentation. Further analysis of blood and synovial fluid by ELISA showed high CXCL10 and CXCL16 in PsA synovial fluid. Differential gene expression of CD4 and CD8 memory T cells revealed increased granzyme K (GZMK) and CXCR3 expression in the synovial fluid T cells compared to blood. Pathway analysis of these GZMK+ T cells showed upregulation of cytotoxic pathways. Further sub-clustering of CD4 and CD8 memory populations revealed unique TCR clonal expansion associated with GZMK. Flow cytometry showed increased CXCR6+ and CXCR3+ T cells in PsA synovial fluid, implicating the CXCR6-CXCL16 and CXCR3-CXCL10 axis in immune cell migration. Together this data suggests that GZMK+ T cells may contribute to inflammation in the joint of PsA patients, after recruitment to the site of inflammation by CD1c+ & CD141+ DCs. Funding Sources NIH T32 National Psoriasis Foundation Topic Categories Immune Mechanisms of Human Disease (HUM)