Osteopontin regulates development and function of invariant natural killer T cells
Osteopontin regulates development and function of invariant natural killer T cells
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DOI：
10.1073/pnas.0806089105
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发表时间：
2008-10-14
影响因子：
11.1
通讯作者：
Uede, Toshimitsu
中科院分区：
文献类型：
--
作者：
Diao, Hongyan;Iwabuchi, Kazuya;Uede, Toshimitsu
不变的自然杀伤T（iNKT）细胞属于桥接先天性和获得性免疫的淋巴细胞亚群。我们证明骨桥蛋白（OPN）参与iNKT细胞的激活。在目前的工作中，我们研究了OPN是否影响iNKT细胞的发育和功能。我们发现，与野生型小鼠相比，OPN缺陷小鼠外周iNKT细胞的数量显着减少。尽管WT和OPN缺陷小鼠的胸腺iNKT细胞数量没有差异，但OPN缺陷小鼠的胸腺内iNKT细胞成熟受损。iNKT细胞功能在OPN缺陷型小鼠中也显著改变，如以下所证明：（i）iNKT细胞受体的下调不足，（h）IL-4产生减少，同时保留IFN-γ的产生，以及（iii）Fas配体（FasL）表达减少，导致Fas/FasL依赖性的针对肝细胞的细胞毒性降低。重要的是，转录因子NFAT 2（活化T细胞的核因子2）和加塔-3的活化受损，而T-bet的活化在OPN缺陷小鼠的iNKT细胞中得以保留。这些数据共同表明，OPN不仅在iNKT细胞的发育中起关键作用，而且在iNKT细胞的功能中也起关键作用。
Invariant natural killer T (iNKT) cells belong to a subset of lymphocytes bridging innate and acquired immunity. We demonstrated that osteopontin (OPN) is involved in the activation of iNKT cells. In the present work, we examined whether OPN affects development and function of iNKT cells. We found that the number of peripheral iNKT cells was significantly reduced in OPN-deficient mice compared with wild-type mice. Although the number of thymic iNKT cells was not different between WT and OPN-deficient mice, intrathymic iNKT cell maturation was impaired in OPN-deficient mice. iNKT cell function was also significantly altered in OPN-deficient mice, as evidenced by (i) deficient down-regulation of iNKT cell receptor, (h) reduction of IL-4 production while preserving production of IFN-gamma, and (iii) reduction of Fas ligand (FasL) expression, leading to reduced Fas/FasL-dependent cytotoxicity against hepatocytes. Importantly, activation of the transcription factors NFAT2 (nuclear factor of activated T cells 2) and GATA-3 was impaired, whereas activation of T-bet was preserved in iNKT cells of OPN-deficient mice. These data collectively indicate that OPN plays a pivotal role not only in the development, but also in the function of iNKT cells.