Ceria nanoparticles promoted the cytotoxic activity of CD8+ T cells by activating NF-κB signaling
Ceria nanoparticles promoted the cytotoxic activity of CD8+ T cells by activating NF-κB signaling
复制标题
二氧化铈纳米颗粒通过激活 NF-kappa B 信号传导促进 CD8( ) T 细胞的细胞毒活性
DOI：
10.1039/c9bm00113a
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发表时间：
2019-06-01
影响因子：
6.6
通讯作者：
Zhou, Xinyuan
中科院分区：
文献类型：
--
作者：
Tang, Shupei;Zhou, Lan;Zhou, Xinyuan
细胞毒性CD8(+) T细胞（ctl）对控制细胞内病原体和癌症至关重要。然而，如何在体外和体内促进CTL细胞的细胞毒性活性仍然是一个很大的未知问题。另一方面，氧化铈纳米颗粒（CNPs）广泛应用于生物医学领域，但CNPs在CTL细胞中的作用尚不清楚。在本研究中，我们发现活化的抗原特异性（P14）和非特异性CD8+ T细胞经CNP处理后产生更多的细胞因子，包括白细胞介素-2 （IL-2）和肿瘤坏死因子- α (tnf - α)，释放更多的效应分子，如颗粒酶B和穿孔素，从而在体外对P14细胞有更高的杀伤活性，在体内对CTL细胞有更强的病毒清除能力。从机制上讲，经过CNP处理的活化P14细胞抑制了活性氧的产生，从而促进了NF-kappa B信号的活性。重要的是，当P14细胞同时被NF-kappa B信号的特异性抑制剂IMD-0354处理时，IL-2和tnf - α产生以及颗粒酶B和穿孔素释放的增加得到了补救，P14细胞最终在体外表现出自然杀伤活性。因此，我们的研究结果表明，CNP治疗提高了CTL细胞的细胞毒活性，为CNP的使用提供了新的思路，并为临床应用，特别是癌症免疫治疗提供了诱人的药理潜力。
Cytotoxic CD8(+) T cells (CTLs) are crucial for controlling intracellular pathogens as well as cancer. However, how to promote the cytotoxic activity of CTL cells in vitro and in vivo remains largely unknown. On the other hand, ceria nanoparticles (CNPs) are widely used in biomedical fields, but the role of CNPs in CTL cells is still unclear. In this study, we found that the activated antigen-specific (P14) and nonspecific CD8+ T cells with CNP treatment both produced more cytokines, including interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha), and released more effector molecules, such as granzyme B and perforin, and then exhibited higher killing activity of P14 cells in vitro and stronger viral clearance capacity of CTL cells in vivo. Mechanistically, the activated P14 cells with CNP treatment inhibited the production of reactive oxygen species, and therefore promoted the activity of NF-kappa B signaling. Importantly, while the P14 cells were simultaneously treated by IMD-0354, a specific inhibitor of NF-kappa B signaling, the increases of IL-2 and TNF-alpha productions and granzyme B and perforin releases were remedied, and the P14 cells eventually exhibited the natural killing activity in vitro. Thus, our results demonstrated that CNP treatment promoted the cytotoxic activity of CTL cells and provide new ideas in the usage of CNPs and fascinating pharmacological potentials for clinical application, especially cancer immunotherapy.