Synovial fluid cells in proteoglycan-induced arthritis contain a myeloid-derived suppressor population (167.21)

Abstract

Abstract Joint damage in rheumatoid arthritis (RA) is largely mediated by synovial fluid (SF) neutrophils. In proteoglycan (PG)-induced arthritis (PGIA), an autoimmune mouse model of RA, SF cells show high expression of the myeloid lineage markers CD11b and Gr-1. The effects of this neutrophil-like SF cell population on the activation of dendritic cells (DCs) or T cells have not been studied in RA or its animal models. We co-cultured SF cells of PGIA mice with bone marrow-derived DCs, and found that levels of MHC II and CD86 expression by DCs decreased significantly in the presences of SF cells. To determine if SF cells also reduced the antigen (Ag)-presenting capacity of the DCs, we added naïve PG-specific TCR transgenic T cells and cognate Ag to the co-cultures. T cells cultured in the presence of SF cells and Ag-loaded DCs showed significant decreases in CD69 expression and proliferation compared to T cells cultured with Ag-loaded DCs only. Arginase-1, a marker of myeloid-derived suppressor cells (MDSCs) was upregulated at both transcriptional and protein levels in SF cells. Expression and activity of arginase-1 were also elevated in spleen cells of arthritic mice as compared to spleen cells of naïve non-arthritic mice. Our results suggest that SF cells in the arthritic joints and spleens of mice with PGIA contain a population of MDSCs, which might have the capacity to suppress autoreactive T cell responses and thus accelerate the resolution of joint inflammation.