Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases
Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases
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DOI：
10.1016/j.immuni.2004.08.012
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发表时间：
2004-10-01
期刊：
影响因子：
32.4
通讯作者：
Uede, T
中科院分区：
文献类型：
--
作者：
Diao, HY;Kon, S;Uede, T
骨桥蛋白（OPN）和自然杀伤T（NKT）细胞在免疫性疾病的发展中发挥作用。我们研究了OPN和NKT细胞之间的功能联系。伴刀豆球蛋白A（Con A）诱导的肝炎是一种特征良好的T细胞介导的肝病小鼠模型。在这里，我们发现NKT细胞分泌OPN，OPN增强NKT细胞活化并触发中性粒细胞浸润和活化。因此，OPN和NKT细胞缺陷小鼠对Con A诱导的肝炎不敏感。此外，通过凝血酶裂解暴露的对OPN的隐蔽表位特异的中和抗体改善了肝炎。这些发现将NKT细胞衍生的OPN确定为治疗炎症性肝病的新靶点。
Both osteopontin (OPN) and natural killer T (NKT) cells play a role in the development of immunological disorders. We examined a functional link between OPN and NKT cells. Concanavalin A (Con A)-induced hepatitis is a well-characterized murine model of T cell-mediated liver diseases. Here, we show that NKT cells secrete OPN, which augments NKT cell activation and triggers neutrophil infiltration and activation. Thus, OPN- and NKT cell-deficient mice were refractory to Con A-induced hepatitis. In addition, a neutralizing antibody specific for a cryptic epitope of OPN, exposed by thrombin cleavage, ameliorated hepatitis. These findings identify NKT cell-derived OPN as a novel target for the treatment of inflammatory liver diseases.