Involvement of H-Ras in the adaptive immunity of Nile tilapia by regulating lymphocyte activation
Involvement of H-Ras in the adaptive immunity of Nile tilapia by regulating lymphocyte activation
复制标题
H-Ras通过调节淋巴细胞活化参与尼罗罗非鱼的适应性免疫
DOI：
10.1016/j.fsi.2019.04.003
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发表时间：
2019
影响因子：
4.7
通讯作者：
Yang Jialong
中科院分区：
文献类型：
--
作者：
Wei Xiumei;Zhao Tianyu;Zhang Yu;Ai Kete;Li Huiying;Yang Jialong
H-Ras是一种鸟苷三磷酸酶（GTPase），作为分子开关，控制包括淋巴细胞活化和功能在内的多个重要细胞过程。然而，在非哺乳动物中，H-Ras对适应性免疫反应的调控机制尚不清楚。在本研究中，我们用nilochromis硬骨鱼模型研究了H-Ras在淋巴细胞活化中的作用。h - fromO。niloticus（On-H-Ras）与其他脊椎动物的基因高度保守。On-H-Ras mRNA在淋巴组织中广泛表达，在肝脏中表达量最高。在感染嗜水气单胞菌后，on - h - ras的转录在第8天被显著诱导，但在第16天恢复到基础水平，提示on - h - ras可能参与了适应性免疫的初次应答。体外T淋巴细胞有丝分裂原PHA激活白细胞后，On-H-Ras mRNA明显上调。同时，淋巴细胞受体信号激动剂PMA和离子霉素刺激白细胞后，H-Ras蛋白水平升高。更重要的是，一旦Ras活性被特异性抑制剂抑制，淋巴细胞活化过程中淋巴细胞活化标志物CD122的上调明显受损。因此，On-H-Ras通过mRNA和蛋白水平调控淋巴细胞活化。总之，我们的研究结果说明了H-Ras通过控制淋巴细胞激活参与硬骨鱼适应性免疫，从而为理解淋巴细胞介导的适应性免疫的进化提供了新的视角。
H-Ras is a guanosine triphosphatase (GTPase), which acts as a molecular switch and controls multiple important cellular processes including lymphocyte activation and function. However, regulatory mechanism of adaptive immune response by H-Ras remains unclear in non-mammalian animals. In the present study, we investigated the involvement of H-Ras in lymphocyte activation with a teleost model Oreochromis niloticus. H-Ras fromO. niloticus(On-H-Ras) is highly conserved with those from other vertebrates. The mRNA of On-H-Ras showed a wide expression pattern in the lymphoid-tissues and with the highest level in liver. After Aeromonas hydrophila infection, transcription of On-H-Ras was significantly induced on day 8 but came back to basal level on day 16, suggesting that On-H-Ras potentially participated in primary response during the adaptive immunity. Furthermore, On-H-Ras mRNA was obviously up-regulated when leukocytes were activated by T lymphocyte mitogen PHA in vitro. Meanwhile, protein level of H-Ras was also augmented once leukocytes were stimulated with lymphocyte receptor signaling agonist PMA and ionomycin. More importantly, once Ras activity was inhibited by specific inhibitor, the up-regulation of lymphocyte activation marker CD122 was obviously impaired during lymphocyte activation process. Therefore, On-H-Ras regulated lymphocyte activation through both mRNA and protein level. Altogether, our results illustrated the involvement of H-Ras in teleost adaptive immunity via controlling lymphocyte activation, and thus provided a novel perspective to understand evolution of the lymphocyte-mediated adaptive immunity.