Inflammatory arthritis increases the susceptibility to acute immune-mediated hepatitis in mice through enhancing leptin expression in T cells.
Inflammatory arthritis increases the susceptibility to acute immune-mediated hepatitis in mice through enhancing leptin expression in T cells.
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DOI：
10.1016/j.molimm.2021.09.015
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发表时间：
2021-10
影响因子：
3.6
通讯作者：
Youyi Wang;Ping Wang;Qishan Xu;Lijun Dong;Yunzhi Liu;Yu Chen;Jia Zhou;Xiao Lu;Daming Zuo;Qingyun Chen
中科院分区：
文献类型：
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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
肝功能异常在炎症性关节炎患者中很常见。然而，确切的机制仍不清楚。本研究通过皮下注射弗氏完全佐剂建立小鼠炎症性关节炎模型，并通过静脉注射刀豆蛋白A(ConA)诱导小鼠急性免疫性肝炎。结果表明，关节炎小鼠比对照组更易患ConA诱导的肝炎，表现为肝坏死增加，血清丙氨酸氨基转移酶活性升高，炎性细胞因子增加。此外，体外实验表明，关节炎小鼠的T细胞对ConA的刺激比正常小鼠更敏感。此外，我们还测定了一种脂肪因子瘦素在关节炎小鼠血清和肝脏T细胞中的水平显著增加。有趣的是，这些数据表明，肝脏T细胞中瘦素表达的增强是关节炎小鼠来源的T细胞对ConA攻击超敏的原因。总之，我们的研究结果表明，瘦素在炎性关节炎和急性免疫介导性肝炎之间的联系中发挥了意想不到的作用，从而为关节炎相关肝功能障碍的临床治疗提供了新的见解。
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, thein vitroassay 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.