T-cell immunoglobulin domain and mucin domain 3 polymorphism affects cytokine expression in different cells and is associated with increased susceptibility to knee osteoarthritis

Abstract

Osteoarthritis (OA) is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. In China, knee OA accounts for the majority of the OA cases. Elevated immune responses and proinflammatory cytokine expressions have been identified in OA patients. Tim-3 plays critical roles in down-regulating T cell responses. Here, we first examined the correlation between Tim-3 polymorphisms and the risk of knee OA. Data showed that the percentage of rs200181745TG (-1622G/T) genotype was significantly higher in knee OA patients compared to the controls (odds ratio [OR]=2.23, 95% confidence interval [CI]: 1.19–4.89, P<0.001). We further investigated the effects of the two Tim-3 polymorphisms on cytokine expressions in different cells. Results showed that subjects with rs200181745TG genotype presented increased mRNA and protein levels of interferon gamma (IFN-γ) from CD4+ T cells (P<0.001), and elevated mRNA level of IFN-γ from CD8+ T cells (P<0.001). However, the Tim-3 polymorphisms did not affect the expression of tumor necrosis factor alpha (TNF-α) in CD4+ and CD8+ T cells. These findings indicate that Tim-3 polymorphism can affect cytokine expression in different cells and is associated with increased susceptibility to knee OA.