CD14+ Dendritic-Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues

We previously reported that CD14+ dendritic-shaped cells exhibit a dendritic morphology, engage in pseudo-emperipolesis with lymphocytes, and express CD90 in the perivascular areas of rheumatoid arthritis (RA) synovial tissues. However, it remains unclear whether these CD14^highCD90^{intermediate(int)} cells function as dendritic cells. In this study, we investigated the dendritic cell-differentiation potential of CD14^highCD90^int cells.

The localization and number of CD14^highCD90^int cells in RA synovial tissues and peripheral blood were examined. The dendritic cell-differentiation potential of CD14^highCD90^int cells was examined by measuring interleukin-6 and tumor necrosis factor-α levels in the supernatant and CD83 and human leukocyte antigen (HLA)-DR expression in the cells after induction of dendritic cell differentiation. Synovial cells were co-cultured with lymphocytes, and the activation of these cells was examined.

CD14^highCD90^int cells were abundant in RA synovial tissues, including the sublining layer and the pannus areas. Patients with untreated and active RA had significantly higher percentages of CD14^highCD90^int cells in the peripheral blood and synovial tissues. In RA synovial cells, inflammatory cytokine levels increased with dendritic cell-differentiation culture, but CD83 and HLA-DR expression were significantly increased in the CD14^highCD90^int cell group. When co-cultured with lymphocytes, cell numbers and inflammatory cytokine levels significantly increased in both groups of synovial cells after dendritic cell induction.

CD14+ cells migrate and spread from the circulating blood to RA synovial tissues while expressing CD90, and CD14^highCD90^int cells in contact with lymphocytes differentiate into HLA-DR+ dendritic cells, which contribute to chronic inflammation in RA.