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

Abstract

OBJECTIVE 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 CD14highCD90intermediate(int) cells function as dendritic cells. In this study, we investigated the dendritic cell-differentiation potential of CD14highCD90int cells. METHODS The localization and number of CD14highCD90int cells in RA synovial tissues and peripheral blood were examined. The dendritic cell-differentiation potential of CD14highCD90int 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. RESULTS CD14highCD90int 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 CD14highCD90int 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 CD14highCD90int 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. CONCLUSION CD14+ cells migrate and spread from the circulating blood to RA synovial tissues while expressing CD90, and CD14highCD90int cells in contact with lymphocytes differentiate into HLA-DR+ dendritic cells, which contribute to chronic inflammation in RA.