RA and PsA synovial tissue single-cell analysis demonstrates differential fibroblast populations with distinct phenotypes and functional capacities

OBJECTIVES: This study determines the phenotypic and functional characteristics that define distinct fibroblast-like synoviocyte (FLS) populations in rheumatoid arthritis (RA) vs psoriatic arthritis (PsA). METHODS: FLS vs THY1⁻ FLS function in RA vs PsA was assessed by flow cytometry, enzyme-linked immunosorbent assay (ELISA), quantitative real -time quantitative polymerase chain reaction (qPCR), and metabolic analysis ex vivo, in vitro, and in the presence of verteporfin (Hippo signalling blockade). RESULTS: FLS, and blockade of this signalling inhibited FLS pathogenic function. CONCLUSIONS: RA and PsA possess distinct FLS populations with unique functional and metabolic properties, which may facilitate improved understanding of disease pathogenesis and therapeutic response.