Inflammatory arthritis increases the susceptibility to acute immune-mediated hepatitis in mice through enhancing leptin expression in T cells

炎症性关节炎通过增强 T 细胞中瘦素的表达,增加小鼠对急性免疫介导性肝炎的易感性

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作者:Youyi Wang, Ping Wang, Qishan Xu, Lijun Dong, Yunzhi Liu, Yu Chen, Jia Zhou, Xiao Lu, Daming Zuo, Qingyun Chen

Abstract

Liver function abnormalities are common in patients with inflammatory arthritis. However, the precise mechanism is still unclear. In this study, inflammatory arthritis was established in mice by subcutaneous injection of complete Freund's adjuvant, and the intravenous injection of concanavalin A (Con A) was employed to induce acute immune-mediated hepatitis in mice. The result showed that the arthritis mice were more susceptible to ConA-induced hepatitis than the control mice, as evidenced by increased hepatic necrosis, elevated serum alanine aminotransferase activity, and raised inflammatory cytokines. Besides, the in vitro assay demonstrated that the T cells from arthritis mice were more sensitive to the Con A stimulation than those from control mice. Moreover, we determined that the level of leptin, a kind of adipokine, was significantly increased in the serum and hepatic T cells of arthritis mice. Interestingly, the data indicated that the enhanced expression of leptin in hepatic T cells is responsible for the hypersensitivity of arthritis mice-derived T cells to Con A challenge. Collectively, our findings demonstrate an unexpected role of leptin in the connection between inflammatory arthritis and acute immune-mediated hepatitis, thus providing new insight into the clinical therapy of arthritis-related liver dysfunction.

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