State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Fish Shellfish Immunol. 2022 Aug;127:419-426. doi: 10.1016/j.fsi.2022.06.044. Epub 2022 Jun 29.
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.
白细胞介素-2 可诱导 T 细胞激酶(ITK)在 T 细胞受体(TCR)信号级联中发挥主要作用,以确保有效的 T 细胞激活和功能。然而,它是否调节早期脊椎动物的 T 细胞反应尚不清楚。在此,我们研究了 ITK 参与淋巴细胞介导的适应性免疫反应及其对尼罗罗非鱼 Oreochromis niloticus T 细胞激活的调节作用。尼罗罗非鱼 ITK(OnITK)的序列和结构与其他脊椎动物的同源物非常保守,这表明其可能具有保守的功能。OnITK mRNA 在淋巴相关组织中广泛表达,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,脾脏淋巴细胞中的 OnITK 在感染后 7 天在转录和翻译水平上均显著上调,表明 OnITK 可能参与了硬骨鱼的初级适应性免疫反应。此外,当用 T 细胞特异性有丝分裂原 PHA 刺激脾脏淋巴细胞时,OnITK mRNA 和蛋白水平均显著升高。更重要的是,用特异性抑制剂处理脾脏淋巴细胞会严重削弱 OnITK 的表达,进而损害 T 细胞激活标志物 IFN-γ、IL-2 和 CD122 的诱导表达,表明 ITK 在调节尼罗罗非鱼 T 细胞激活中起关键作用。总之,我们的结果表明 ITK 参与了罗非鱼的淋巴细胞介导的适应性免疫反应,并且是硬骨鱼 T 细胞激活所必需的。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。