IL-17C/IL-17RE Augments T Cell Function in Autoimmune Hepatitis
IL-17C/IL-17RE Augments T Cell Function in Autoimmune Hepatitis
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DOI：
10.4049/jimmunol.1600977
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发表时间：
2017-01-15
影响因子：
4.4
通讯作者：
Dong, Chen
中科院分区：
文献类型：
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作者：
Huang, Jinling;Yuan, Qing;Dong, Chen
自身免疫性肝炎是一个全球性的健康问题，也是导致死亡的重要原因。然而，该疾病的病因在很大程度上尚不明确，这导致治疗效果不佳以及疾病进展无法控制。在这项研究中，我们证明了白细胞介素 - 17C/白细胞介素 - 17受体E轴在刀豆蛋白A诱导的肝炎中的重要功能。在人类和小鼠自身免疫性肝炎的肝脏样本中均检测到白细胞介素 - 17C表达升高。肝细胞产生的白细胞介素 - 17C及其在肝脏驻留T细胞上的特异性受体白细胞介素 - 17受体E，均被发现在刀豆蛋白A诱导的肝损伤中是必需的。从机制上讲，白细胞介素 - 17C通过肝内CD4 + T细胞增强白细胞介素 - 2的表达，从而促进自然杀伤细胞的活化和肝损伤。据我们所知，我们的研究结果首次明确了白细胞介素 - 17C/白细胞介素 - 17受体E在自身免疫性肝炎中不可或缺的作用；该轴可能作为治疗这种疾病的一个新的药物靶点。
Autoimmune hepatitis is a worldwide health problem and significant cause of mortality. However, the disease etiology is largely unknown, which accounts for ineffective treatment and uncontrolled disease progression. In this study, we demonstrated the functional importance of the IL-17C/IL-17RE axis in Con A-induced hepatitis. Elevated IL-17C expression was detected in liver samples of both human and mouse autoimmune hepatitis. IL-17C, produced by hepatocytes, and its specific receptor IL-17RE on liver-resident T cells were both found to be required in Con A-induced liver damage. Mechanistically, IL-17C augmented the expression of IL-2 by intrahepatic CD4+ T cells to promote NK cell activation and liver damage. To our knowledge, our findings thus for the first time defined the indispensable role of IL-17C/IL-17RE in autoimmune hepatitis; this axis may serve as a novel drug target for the treatment of this disease.