Characterization of synovial CD16+ monocytes affecting inflammatory T-cell response in rheumatoid arthritis.

Abstract

Monocytes play critical roles in the pathogenesis of chronic inflammatory diseases, including autoimmunity as well as in the innate response to infections. Human monocytes are heterogeneous and generally classified into three subsets based on CD14 and CD16 expression. Although increasing evidences suggest that three monocyte subsets have distinct functions in inflammatory conditions, little is known about their roles in pathogenesis of autoimmune diseases. To address this issue, I investigated the phenotypic and functional characteristics of monocytes in the synovial fluid (SF) and peripheral blood (PB) from patients with rheumatoid arthritis (RA). CD16 expression on CD14+ monocytes in the SF was significantly increased compared with the PB of RA patients and healthy controls, whereas CD14dimCD16+ monocytes were rarely observed in the SF. The majority of synovial monocytes constitutively expressed CD80, while peripheral monocytes did not express CD80 without stimulation. In addition, the expression of membrane-bound IL-15 was markedly elevated in the RA patients. The TLR expression between peripheral monocyte and synovial monocytes were distinct, monocytes from synovial fluid had increased TLR levels generally. To explore how synovial monocytes gain unique properties, PB monocytes were stimulated with various cytokines and TLR ligands. Interestingly, TGF-β is a potent inducer of CD16 expression on CD14+ monocytes, whereas expressions of CD80 and membrane-bound IL-15 were significantly elevated by IFN-γ exerting a synergistic effect with IL-15. The synovial monocytes were found to significantly promote Th17 and Th1 responses in vitro, compared with PB monocytes from RA patients. The findings in this study suggest the possible role for cytokine milieu of the SF in giving unique features to synovial monocytes and their important roles in affecting inflammatory T-cell response in RA.