What question did this study set out to answer?

The research aims to identify and compare the phenotypic and functional characteristics of fibroblast-like synoviocytes in rheumatoid arthritis and psoriatic arthritis.

April 14, 2026Open Access

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

Key Points

The research aims to identify and compare the phenotypic and functional characteristics of fibroblast-like synoviocytes in rheumatoid arthritis and psoriatic arthritis.
Conducted single-cell RNA sequencing and multiparametric flow cytometry analysis on synovial cell suspensions from RA and PsA.
Assessed FLS function using flow cytometry, ELISA, qPCR, and metabolic analysis across various conditions.
Identified dominant FLS populations and their expressions of immune and metabolic markers.
Significant increases in immune markers in RA FLS, including HLA-DR, YAP, and Cad11 (P < .05).
Increased CD55 expression in PsA-FLS (P < .001).
Differential dominance of THY1 + and THY1 FLS populations in RA and PsA, respectively (P < .05).
Correlation found between THY1 + FAP + FLS and disease activity scores in RA (r = 0.55, P < .05).
Distinct FLS populations identified with significant differences in immune and metabolic markers between RA and PsA.

Abstract

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: Single-cell RNA sequencing and multiparametric flow cytometry analysis (21 markers) were performed on RA and PsA synovial cell suspensions to determine FLS phenotype/function.Podoplanin (PDPN) + FLS and sorted THY1 + 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: Flow analysis of PDPN + FLS demonstrated significant increases in human leukocyte antigen (HLA)-DR + , yes-associated protein (YAP) + , cadherin 11 (Cad11) + , and phosphorylated protein S6 + FLS in RA (all P < .05),while CD55 was increased in PsA-FLS (P < .001).Polyfunctionality demonstrated enhanced coexpression of Cad11 + CD44 + HLA-DR + ICAM-1 + FLS (P < .01)and CD44 + HLA-DR + ICAM-1 + VCAM-1 + FLS (P < .05) in RA, whereas PsA-FLS exhibited increased coexpression of pAKT + pmTOR + (P < .01).THY1 + FLS populations were dominant in RA (P < .05),while THY1 FLS were dominant in PsA (P < .05),with differential angiogenic, chemokine, and matrix metalloproteinase expression observed.THY1 + FAP + FLS correlated with disease activity score (DAS28) (r = 0.55, P < .05)and synovitis (r = 0.54, P < .05).Further flow analysis identified 6 main distinct FLS populations, with enrichment of THY1 + CD34CD55FAP + FLS and THY1 + CD34 + CD55FAP + FLS in RA (P < .05),while PsA displayed enrichment of THY1 + CD34 -CD55 + FAP + FLS (P < .05)and THY1CD34CD55 + FAP + FLS (P < .001).Immune/adhesive markers were significantly higher in RA subpopulations, whereas metabolic/osteogenic markers were higher in PsA subpopulations.

Ask AI

Helpful

Bookmark

View Full Paper