Monocytes function as crucial innate effectors during inflammation. Human monocytes can be divided into three distinct subsets based on CD14 and CD16 expression. Accumulating evidences suggest that three monocyte subsets have distinct functions in inflammatory response. We investigated the characteristics of monocytes in synovial fluid (SF) of RA patients. CD16 expression on CD14++ monocytes in the SF was significantly increased compared with that in the peripheral blood (PB) of RA patients and healthy control (HC). Microarray data showed that 3,134 genes were differentially expressed in SF monocytes compared with PB monocytes. Among the genes, CD80 and CD276 expression were significantly elevated on SF monocytes, while PB monocytes of RA and HC did not express both of them without stimulation. CD80 and CD276 belong to the B7 family, which plays a checkpoint role for modulating T-cell responses. To explore how SF monocytes gain unique properties, PB monocytes were stimulated with various cytokines and TLR ligands. TGF-β was a potent inducer of CD16 expression on monocytes, whereas expressions of CD80 and CD276 were markedly elevated by IFN-γ and GM-CSF, respectively. In vitro assay, SF monocytes were found to significantly promote Th17 and Th1 responses, compared with PB monocytes of RA patients. Our findings suggest the possible role for cytokine milieu of the SF in giving unique features to SF monocytes and their crucial roles in affecting inflammatory T-cell response in RA

2014