High Interleukin-37 (IL-37) Expression and Increased Mucin-Domain Containing-3 (TIM-3) on Peripheral T Cells in Patients with Rheumatoid Arthritis

BACKGROUND: Anti-inflammatory mediators such as mucin-domain containing-3 (TIM-3) and IL-37 play an important role in the regulation of Th1-mediated immunity. This study was designed to investigate the proportions of various T cell subsets and monocytes in the peripheral blood of rheumatoid arthritis (RA) patients, as well as the level of TIM-3 on these cells and serum cytokine levels. MATERIAL/METHODS: We enrolled 59 RA patients and 46 age- and sex-matched healthy controls in this study. The proportion of T cells and TIM-3 expression on these T cells were determined by flow cytometry. Cytokine levels in serum were determined by ELISA. RESULTS: Compared with the healthy controls, the proportions of CD3(+)CD4(+) T cells and CD3(+)CD4(+)CD25(+)CD127(low) T cells in the peripheral blood were significantly higher in RA patients. However, RA patients had significantly lower proportions of CD3(+)CD8(+) T cells and CD3(+)CD4(−)CD8(−) T cells. TIM-3 was highly expressed on CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD4(+)CD25(+)CD127(low), and CD3(+)CD4(−)CD8(−) T cells, as well as CD14(+) monocytes, in RA patients. Nevertheless, no correlation between TIM-3 level and an RA disease activity score of 28 was found. The elevated serum levels of IL-6 and IL-37 were positively correlated with tumor necrosis factor-α (TNF-α). CONCLUSIONS: Both pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory mediators (TIM-3 and IL-37) simultaneously contribute to the pathogenesis of RA. TIM-3 and IL-37 may be used as potential biomarkers of active RA.