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T 细胞分泌的颗粒酶 B 参与罗非鱼的抗细菌免疫反应。

Granzyme B secreted by T cells is involved in anti-bacterial immune response of tilapia.

机构信息

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.

出版信息

Fish Shellfish Immunol. 2024 Oct;153:109865. doi: 10.1016/j.fsi.2024.109865. Epub 2024 Aug 28.

Abstract

Secreted by natural killer cells and cytotoxic T lymphocytes, Granzyme B is involved in regulating the adaptive immune response in vertebrates and plays a pivotal role in resisting virus invasion and removing pathogens. Although it had been extensively studied in mammals, the involvement of Granzyme B in adaptive immune response of early vertebrates remained elusive. In this study, we investigated the Granzyme B in Oreochromis niloticus (OnGrB), found that its function domain was conserved. Additionally, OnGrB was widely expressed in various tissues and could respond to T-cell activation in vitro at the transcriptional level. Furthermore, we prepared the recombinant OnGrB (rOnGrB) as an immunogen to develop a mouse anti-OnGrB monoclonal antibody (mAb). Using this anti-OnGrB mAb as a tool, we explored the expression of OnGrB in the adaptive immune response of tilapia. Our findings revealed that T cell was a significant source of OnGrB production, the expression of OnGrB at the protein level and the proportion of OnGrB  T cells increased after both T cell activation in vitro and infection with Edwardsiella piscicida in vivo. More importantly, our findings also preliminarily illuminated that p65 could regulate the transcriptional activity of OnGrB. These results indicated that OnGrB was involved in the adaptive immunity of tilapia and played a critical role in T cell function in teleost. Our study provided theoretical support and new perspectives for understanding adaptive immunity in teleost.

摘要

由自然杀伤细胞和细胞毒性 T 淋巴细胞分泌的 Granzyme B 参与调节脊椎动物的适应性免疫反应,并在抵抗病毒入侵和清除病原体方面发挥关键作用。尽管在哺乳动物中已经对其进行了广泛研究,但 Granzyme B 在早期脊椎动物适应性免疫反应中的参与仍不清楚。在本研究中,我们研究了罗非鱼(OnGrB)中的 Granzyme B,发现其功能域保守。此外,OnGrB 在各种组织中广泛表达,并能在体外 T 细胞激活时在转录水平上做出反应。此外,我们制备了重组 OnGrB(rOnGrB)作为免疫原来开发一种抗 OnGrB 的小鼠单克隆抗体(mAb)。使用这种抗 OnGrB mAb 作为工具,我们探讨了 OnGrB 在罗非鱼适应性免疫反应中的表达。我们的研究结果表明,T 细胞是 OnGrB 产生的重要来源,在体外 T 细胞激活和体内感染爱德华氏菌后,OnGrB 的蛋白水平表达和 OnGrB+T 细胞的比例均增加。更重要的是,我们的研究结果还初步表明 p65 可以调节 OnGrB 的转录活性。这些结果表明 OnGrB 参与了罗非鱼的适应性免疫反应,并在硬骨鱼 T 细胞功能中发挥关键作用。我们的研究为理解硬骨鱼适应性免疫提供了理论支持和新视角。

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