Interleukin-2 inducible T cell kinase (ITK) may participate in the anti-bacterial immune response of Nile tilapia via regulating T-cell activation
Interleukin-2 inducible T cell kinase (ITK) may participate in the anti-bacterial immune response of Nile tilapia via regulating T-cell activation
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白细胞介素2诱导性T细胞激酶(ITK)可能通过调节T细胞活化参与尼罗罗非鱼的抗菌免疫反应
DOI：
10.1016/j.fsi.2022.06.044
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发表时间：
2022
影响因子：
4.7
通讯作者：
Jialong Yang
中科院分区：
文献类型：
--
作者：
Wei Liang;Kunming Li;Qian Zhang;Kang Li;Kete Ai;Jiansong Zhang;Xinying Jiao;Jiaqi Li;Xiumei Wei;Jialong Yang
白细胞介素2诱导的T细胞激酶(ITK)在T细胞受体(TCR)信号通路中起主导作用，以确保T细胞的有效激活和功能。然而，它是否调节早期脊椎动物的T细胞反应仍不清楚。在此，我们研究了ITK在尼罗罗非鱼淋巴细胞介导的适应性免疫反应中的作用及其对T细胞活化的调节。尼罗非鱼ITK(OnITK)的序列和结构与其他脊椎动物的同源物高度保守，提示其潜在的保守功能。OnITK基因在淋巴相关组织中广泛表达，且在外周血中表达水平相对最高。一旦尼罗罗非鱼感染爱德华氏菌，7d后脾淋巴细胞中OnITK的转录和翻译水平均显著上调，提示OnITK可能参与了硬骨鱼的初级适应性免疫反应。此外，T细胞特异性有丝分裂原PHA刺激脾淋巴细胞后，OnITK的mRNA和蛋白水平显著升高。更重要的是，经特异性抑制剂处理的脾淋巴细胞显著抑制了OnITK的表达，进而削弱了T细胞活化标志物干扰素-γ、IL-2和CD122的诱导表达，表明ITK在调节尼罗罗非鱼T细胞活化中起着关键作用。综上所述，我们的结果表明，ITK参与了罗非鱼淋巴细胞介导的适应性免疫，并在硬骨鱼的T细胞激活中起着不可或缺的作用。因此，我们的发现为理解早期脊椎动物T细胞免疫的调节机制以及适应性免疫系统的进化提供了新的证据。
Interleukin-2 inducible T cell kinase (ITK) plays a predominant role in the T-cell receptor (TCR) signaling cascade to ensure valid T-cell activation and function. Nevertheless, whether it regulates T-cell response of early vertebrates remains unknown. Herein, we investigated the involvement of ITK in the lymphocyte-mediated adaptive immune response, and its regulation to T-cell activation in the Nile tilapia Oreochromis niloticus. Both sequence and structure of O. niloticus ITK (OnITK) were remarkably conserved with its homologues from other vertebrates, implying its potential conserved function. OnITK mRNA was extensively expressed in lymphoid-related tissues, and with the relative highest level in peripheral blood. Once Nile tilapia was infected by Edwardsiella piscicida, OnITK in splenic lymphocytes was significantly up-regulated on 7-day post infection at both transcription and translation levels, suggesting that OnITK might involve in the primary adaptive immune response of teleost. Furthermore, upon splenic lymphocytes were stimulated by T-cell specific mitogen PHA, OnITK mRNA and protein levels were dramatically elevated. More importantly, treatment of splenic lymphocytes with specific inhibitor significantly crippled OnITK expression, which in turn impaired the inducible expression of T-cell activation markers IFN-γ, IL-2 and CD122, indicating the critical roles of ITK in regulating T-cell activation of Nile tilapia. Taken together, our results suggest that ITK takes part in the lymphocyte-mediated adaptive immunity of tilapia, and is indispensable for T-cell activation of teleost. Our findings thus provide novel evidences for understanding the mechanism regulating T-cell immunity of early vertebrates, as well as the evolution of adaptive immune system.