美国德克萨斯大学西南医学中心Bruce Beutler团队取得最新进展。他们发现Schlafen 2（SLFN2）保护tRNA免受应激诱导的裂解对于T细胞介导的免疫至关重要。该研究于2021年5月14日发表于国际一流学术期刊《科学》杂志上。

他们表明，这些活性氧（ROS）触发氧化应激反应，导致翻译抑制。SLFN2可以抵抗这种反应，后者直接结合转移RNA（tRNA），以保护它们免受核糖核酸酶血管生成素的切割。T细胞特异性SLFN2缺陷导致tRNA片段的积累，从而抑制翻译并促进应激颗粒的形成。T细胞受体刺激后，白细胞介素2受体β（IL-2Rβ）和IL-2Rγ不能被翻译上调，从而使缺乏SLFN2的T细胞对白细胞介素2的促有丝分裂作用不敏感。SLFN2赋予抵抗通常由T细胞活化诱导的ROS介导的翻译抑制作用的抗性，从而实现T细胞扩增和免疫所必需的强大蛋白质合成。

据悉，活跃的T细胞中ROS的增加是由于被诱导支持T细胞增殖和分化的代谢活性所致。

附：英文原文

Title: SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell–mediated immunity

Author: Tao Yue, Xiaoming Zhan, Duanwu Zhang, Ruchi Jain, Kuan-wen Wang, Jin Huk Choi, Takuma Misawa, Lijing Su, Jiexia Quan, Sara Hildebrand, Darui Xu, Xiaohong Li, Emre Turer, Lei Sun, Eva Marie Y. Moresco, Bruce Beutler

Issue&Volume: 2021/05/14

Abstract: Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell–specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor β (IL-2Rβ) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2’s mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

DOI: 10.1126/science.aba4220

Source: https://science.sciencemag.org/content/372/6543/eaba4220