Background/Purpose: Monocytes plays a role in juvenile idiopathic arthritis (JIA). CD14^dim monocytes have modulatory effects in innate and adaptive immune responses. Siglec-10, which is highly expressed on CD14^dim monocytes, functions as an inhibitory receptor within the innate immune system. The interaction between Siglec-10 and its ligand CD24 could prevent tissue damage-induced immune responses. Siglec-G (murine Siglec-10 homolog) knockout mice developed increased clinical disease in mouse arthritis model, which suggests a role of Siglec-G/10 in pathogenesis of arthritis.  IL-29 is a member of type III IFN family. Besides its antiviral and antitumor function, IL-29 also has immune-regulation function. In this study, we investigated the expression of Siglec-10 on CD14^dim monocytes from synovial fluid (SF) and peripheral blood (PB) of JIA patients and assessed IL-29 as a candidate cytokine produced from the Siglec10-CD24 interaction.

Methods: A total of 42 patients, including 24 JIA, 10 systemic lupus erythematosus (SLE) and 8 controls were included. Siglec-10⁺CD14^dim monocytes were sorted by flow cytometry to culture with or without human CD24 fusion protein. The expression of Siglec-10 on PB and SF monocytes was measured by flow cytometry. IL-29 mRNA expression was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction.

Results:  The percentage of synovial Siglec-10⁺CD14^dim monocytes of JIA patients was significantly decreased compared with that from peripheral blood. Furthermore, the expression of Siglec-10 (Mean fluorescent intensity, MFI) was significantly lower on SF CD14^dim monocytes when compared with PB CD14^dim monocytes. Although the expression of Siglec-10 on PB CD14^dim monocytes was similar in JIA, SLE and the control subjects, the percentage of Siglec-10⁺CD14^dim monocytes from PB was higher in JIA patients compared with SLE patients and controls. IL-29 mRNA transcript in Siglec-10⁺CD14^dim monocytes cultured with CD24 fusion protein in vitro was increased, relative to controls cultured without CD24 fusion protein.

Conclusion: Interaction between Siglec-10 and CD24 on CD14^dim monocytes may trigger the production of IL-29 which may mediate immunoregulatory function. The reduction of SF Siglec10⁺CD14^dim monocytes in JIA patients and the reduction of Siglec-10 expression on these cells may have contributed to the pathogenesis of JIA.

Figure. A. Representative staining of mononuclear cells with CD14 and Siglec-10 in PB (left) and SF (right) from the same JIA patient at the same day. B. The percentages of Siglec-10⁺CD14^dim monocytes in CD14^dim monocytes in different groups. C. The MFI of Siglec-10 on Siglec-10⁺CD14^dim monocytes in different groups.  *P<0.05,  **** P<0.0001. MFI, mean fluorescent intensity; JIA, juvenile idiopathic arthritis; PB, peripheral blood; SF, synovial fluid.