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

Abstract

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. 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. We observed no changes in the histopathology or the overall distribution of broadly classified cell populations (myeloid, lymphoid, and stromal) before and after tolDC administration. Furthermore, the proportions of CD4⁺ and CD8⁺ T cells were not altered, with no indication that tolDC had induced regulatory T cells within the synovium. However, we found a significant increase in a subset of myeloid cells expressing high levels of the inflammation resolution marker Mer tyrosine kinase (MerTK^High), which positively correlated with tolDC dose. Moreover, the percentages of total MerTK⁺ myeloid cells inversely correlated with arthroscopic synovitis scores at both time points. The tolDC-induced increase in synovial Myeloid MerTK^High cells may have local immune modulatory effects and provide promising evidence for an effect of tolDC treatment on the synovial immune landscape.