Intra-articular injection of autologous tolerogenic dendritic cells modifies the synovial immune landscape in rheumatoid and inflammatory arthritis

OBJECTIVES: In our previously reported trial of intra-articular tolerogenic dendritic cells (tolDC) as a treatment to restore immune tolerance in autoimmune arthritis, high doses of cells appeared to stabilise knee symptoms, although no systemic clinical or immunomodulatory effects were observed. We therefore sought to understand how tolDC affected the local synovial immune landscape. METHODS: Synovial biopsies were taken at baseline and 14 days after intra-articular injection of tolDC or, as a control, saline washout. Histopathological analyses (Krenn evaluation and pathotype) and multiparametric imaging mass cytometry (IMC) were performed on paired synovial tissues from 7 participants (5 tolDC-treated and 2 controls), selected based on tissue availability at both time points. The IMC panel included 27 antibodies defining lymphoid, myeloid, and stromal cells. RESULTS: myeloid cells inversely correlated with arthroscopic synovitis scores at both time points. CONCLUSIONS: cells may have local immune modulatory effects and provide promising evidence for an effect of tolDC treatment on the synovial immune landscape.