Acute liver injury is a common pathological basis for a variety of acute liver diseases in the clinic, which can eventually lead to liver fibrosis and even liver failure. In this study, we found that T cell Ig and mucin domain protein 3 (Tim-3) and TLR4 receptors play important roles in CCl4-induced acute liver injury. Tim-3 is a negative regulator that is expressed by T cells and macrophages. Using antibodies against Tim-3 (anti-Tim-3 Ab), we studied the Tim-3 signal in an animal model of acute liver injury and found that a large number of inflammatory factors were upregulated. In vitro experimental data shown that anti-Tim-3 Ab treatment increased interferon-ɣ production by concanavalin A (ConA)-stimulated spleen T cells, and we found that the expression level of interleukin (IL)-6 was increased in a macrophage/spleen T cell coculture system, while administration of galectin-9 (Gal-9, a Tim-3 ligand) reduced the IL-6 production. This indicates the importance of the Tim-3/Gal-9 signalling pathway in maintaining hepatic homeostasis. The Tim-3 signalling pathway inhibits TLR4-mediated NF-κB activity, and an anti-Tim-3 Ab does not affect the liver injury in TLR4-deficient mice. Regulation between Tim-3 and TLR4 determines the severity of liver damage. The negative regulation of Tim-3 reflects the protective mechanisms of patients with impaired liver function, and these results provide important information about innate and adaptive responses in the regulation of liver damage. This finding is potentially important for the study of early liver injury.

中文翻译：

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TLR4和T细胞Ig粘蛋白3的交叉调控决定了CCl4诱导的小鼠模型中肝损伤的严重性。

急性肝损伤是临床上各种急性肝病的常见病理基础，最终可能导致肝纤维化甚至肝衰竭。在这项研究中，我们发现T细胞Ig和粘蛋白结构域蛋白3（Tim-3）和TLR4受体在CCl4诱导的急性肝损伤中起重要作用。Tim-3是一种负调节剂，由T细胞和巨噬细胞表达。使用针对Tim-3的抗体（抗Tim-3 Ab），我们在急性肝损伤动物模型中研究了Tim-3信号，发现大量炎症因子被上调。体外实验数据显示，抗Tim-3 Ab处理可增加伴刀豆球蛋白A（ConA）刺激的脾T细胞产生的干扰素-β，我们发现白细胞介素（IL）-6的表达水平在巨噬细胞/脾T细胞共培养系统 而施用半乳凝素9（Gal-9，Tim-3配体）则可降低IL-6的产生。这表明Tim-3 / Gal-9信号通路在维持肝稳态中的重要性。Tim-3信号通路抑制TLR4介导的NF-κB活性，而抗Tim-3 Ab不会影响TLR4缺陷小鼠的肝损伤。Tim-3和TLR4之间的调节决定了肝损害的严重程度。Tim-3的负调节反映了肝功能受损患者的保护机制，这些结果提供了有关调节肝损伤的先天性和适应性反应的重要信息。这一发现对于早期肝损伤的研究可能具有重要意义。这表明Tim-3 / Gal-9信号通路在维持肝稳态中的重要性。Tim-3信号通路抑制TLR4介导的NF-κB活性，而抗Tim-3 Ab不会影响TLR4缺陷小鼠的肝损伤。Tim-3和TLR4之间的调节决定了肝损害的严重程度。Tim-3的负调节反映了肝功能受损患者的保护机制，这些结果提供了有关调节肝损伤的先天性和适应性反应的重要信息。这一发现对于早期肝损伤的研究可能具有重要意义。这表明Tim-3 / Gal-9信号通路在维持肝稳态中的重要性。Tim-3信号通路抑制TLR4介导的NF-κB活性，而抗Tim-3 Ab不会影响TLR4缺陷小鼠的肝损伤。Tim-3和TLR4之间的调节决定了肝损害的严重程度。Tim-3的负调节反映了肝功能受损患者的保护机制，这些结果提供了有关调节肝损伤的先天性和适应性反应的重要信息。这一发现对于早期肝损伤的研究可能具有重要意义。Tim-3和TLR4之间的调节决定了肝损害的严重程度。Tim-3的负调节反映了肝功能受损患者的保护机制，这些结果提供了有关调节肝损伤的先天性和适应性反应的重要信息。这一发现对于早期肝损伤的研究可能具有重要意义。Tim-3和TLR4之间的调节决定了肝损害的严重程度。Tim-3的负调节反映了肝功能受损患者的保护机制，这些结果提供了有关调节肝损伤的先天性和适应性反应的重要信息。这一发现对于早期肝损伤的研究可能具有重要意义。