Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
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 responses. Here we investigated the characteristics of monocytes in synovial fluid (SF) of rheumatoid arthritis (RA) patients.
Monocytes and T cells were separated from the peripheral blood (PB) and SF obtained from patients with RA and analyzed by using flow cytometry. For global transcriptome analysis of pathogenic monocytes in RA, we performed a microarray analysis of SF and PB monocytes from the same RA patients and PB monocytes of healthy control (HC).
CD16 expression on CD14++ monocytes in the SF was significantly increased compared with that in the PB of RA patients and HC. Microarray data showed that 3,134 genes were differentially expressed in SF monocytes compared with PB monocytes from RA and HC. 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 is a potent inducer of CD16 expression on CD14++ 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 synovial fluid in giving unique features to SF monocytes and their cardinal roles in affecting inflammatory T-cell response in RA.
S. W. Kang,
S. C. Shim,
I. S. Yoo,
S. J. Yoo,
S. T. Song,
B. R. Yoon,
W. W. Lee,
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/functional-phenotype-of-synovial-monocytes-modulating-inflammatory-t-cell-response-in-rheumatoid-arthritis/