Expression of human TIM-3 and its correlation with disease activity in rheumatoid arthritis

Objective: T-cell immunoglobulin-and mucin-domain-containingmolecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell-mediated immunity. This study was undertaken to investigate the expressions of TIM-3 and its ligand galectin 9 (Gal-9) with respect to disease activity in rheumatoid arthritis (RA). Methods: Blood was collected from 39 RA patients and 31 healthy controls. Blood leucocyte TIM-3 and Gal-9 mRNA levels and RA disease activity were determined. Synovial tissue (ST) from five RA patients and five osteoarthritis (OA) patients were examined for TIM-3 mRNA expression and were also analysed for TIM-3 by immunohistology. Results: TIM-3 mRNA expression was significantly higher in the ST of RA patients than in the ST of OA patients. TIM-3 was expressed in the synovial sublining area in ST of RA patients but not in OA ST. TIM-3 mRNA expression from peripheral blood mononuclear cells (PBMCs) of RA patients was negatively correlated with the 28-joint Disease Activity Score (DAS28). Gal-9 mRNA level in PBMCs of RA patients was higher than in healthy controls, and was significantly higher in patients with low disease activity compared to those with moderate to high disease activity. Gal-9 mRNA expression in PBMCs of RA patients was positively correlated with forkhead box P3 (FoxP3) mRNA expression. Conclusion: TIM-3 and its interaction with Gal-9 are closely associated with RA disease activity and may play an important role in the pathogenesis of RA. In addition to the negative regulatory effect of Gal-9 mediated through the TIM-3-Gal-9 pathway, Gal-9 may exert its suppressive effect on RA disease activity by modulation of regulatory T (Treg) cells.