The involvement of TNF-α and TNF-β as proinflammatory cytokines in lymphocyte-mediated adaptive immunity of Nile tilapia by initiating apoptosis
The involvement of TNF-α and TNF-β as proinflammatory cytokines in lymphocyte-mediated adaptive immunity of Nile tilapia by initiating apoptosis
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TNF-α和TNF-β作为促炎细胞因子通过启动细胞凋亡参与尼罗罗非鱼淋巴细胞介导的适应性免疫
DOI：
10.1016/j.dci.2020.103884
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发表时间：
2021-02-01
影响因子：
2.9
通讯作者：
Yang, Jialong
中科院分区：
文献类型：
--
作者：
Li, Kang;Qiu, Hong;Yang, Jialong
肿瘤坏死因子（tumor necrosis factors，TNFs）是一种多效性细胞因子，在机体内环境的稳定和疾病的发病机制中具有重要作用。最近的进展表明，TNF也参与了适应性免疫应答的调节。然而，关于TNF如何参与和调节早期脊椎动物的适应性免疫应答的知识仍然有限。在本研究中，我们确定了两个异构体的TNF，TNF-α和TNF-β，从尼罗罗非鱼（On-TNF-α和β）。在分析序列特征后，我们研究了它们在该鱼类适应性免疫应答中的调节作用。On-TNF-α和β与其他脊椎动物的同源物相比在进化上是保守的。两种TNF在O. niloticus中表达量最高，在鳃中表达量相对较高。无乳链球菌感染后，小鼠脾淋巴细胞On-TNF-α和TNF-β的mRNA水平在获得性免疫的初级应答阶段显著上调。同时，在细菌感染后的适应性免疫阶段，脾淋巴细胞中的TNF蛋白也显著升高。这些结果表明On-TNF-α和TNF-β可能参与尼罗罗非鱼的适应性免疫应答。此外，一旦脾淋巴细胞被T细胞特异性丝裂原PHA激活，OnTNF-α和β转录明显增加。更重要的是，重组On-TNF-α和On-TNF-β均能诱导尼罗罗非鱼头肾白细胞凋亡。On-TNF-β而非On-TNF-α通过激活caspase-8促进靶细胞凋亡。总之，本研究揭示了TNF-α和TNF-β通过启动细胞凋亡参与了尼罗罗非鱼淋巴细胞介导的适应性免疫应答，为研究硬骨鱼适应性免疫的调控机制提供了新的视角。
Tumor necrosis factors (TNFs) are pleiotropic cytokines with important functions in homeostasis and disease pathogenesis. Recent advances have shown that TNFs are also involved in the regulation of adaptive immune responses. However, the knowledge about how TNF participates in and regulates adaptive immune response in early vertebrates is still limited. In present study, we identified two isoforms of TNF, TNF-alpha and TNF-beta, from Nile tilapia Oreochromis niloticus (On-TNF-alpha and beta). After analyzing the sequence characteristics, we investigated their regulatory roles in adaptive immune response of this fish species. On-TNF-alpha and beta are evolutionarily conserved compare with their homologs from other vertebrates. Both TNFs were distributed in a wide range of tissues in O. niloticus, and with relative higher expression level in gill. After the animals were infected by Streptococcus agalactiae, mRNA levels of On-TNF-alpha and TNF-beta in spleen lymphocytes were significantly upregulated during the primary response stage of adaptive immunity. Meanwhile, both TNF proteins in spleen lymphocytes were also dramatically elevated during the adaptive immune stage after bacterial infection. These results indicate the potential participation of On-TNF-alpha and TNF-beta in adaptive immune response of Nile tilapia. Furthermore, OnTNF-alpha and beta transcripts were obviously augmented, once spleen lymphocytes were activated by T cell-specific mitogen PHA. More importantly, both recombinant On-TNF-alpha and beta could induce the apoptosis of head kidney leukocytes of Nile tilapia. And On-TNF-beta but not On-TNF-alpha promoted the apoptosis by activating caspase-8 in the target cells. Altogether, our study revealed that TNF-alpha and TNF-beta participated in the lymphocyte mediated adaptive immune response of Nile tilapia by initiating the apoptosis, and thus shed novel perspective for the regulatory mechanism of adaptive immunity in teleost.