Over the past several years, SIRT5 has attracted considerable attention in metabolic regulation. However, the function of SIRT5 in tumorigenesis by regulating tumor microenvironment is poorly understood. In this work, we found that Sirt5 knockout mice were resistant to AOM and DSS-induced colitis-associated colorectal tumorigenesis and the level of IFN-γ in their tumor microenvironment was higher. Additionally, proteome and network analysis revealed that SIRT5 was important in the T cell receptor signaling pathway. Furthermore, we determined that a deficiency of Sirt5 induced stronger T cell activation and demonstrated that SIRT5 played a pivotal role in regulating the differentiation of CD4⁺ regulatory T (Treg) cells and T helper 1 (Th1) cells. An imbalance in the lineages of immunosuppressive Treg cells and the inflammatory Th1 subsets of helper T cells leads to the development of colon cancer. Our results revealed a regulatory role of SIRT5 in T cell activation and colorectal tumorigenesis.

中文翻译：

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SIRT5通过调节T细胞活性促进大肠癌的生长。

在过去的几年中，SIRT5在代谢调控中引起了相当大的关注。但是，对SIRT5通过调节肿瘤微环境在肿瘤发生中的功能了解甚少。在这项工作中，我们发现Sirt5基因敲除小鼠对AOM和DSS诱导的结肠炎相关的结肠直肠肿瘤发生具有抗性，并且其肿瘤微环境中的IFN- γ水平更高。此外，蛋白质组和网络分析表明SIRT5在T细胞受体信号传导途径中很重要。此外，我们确定Sirt5的缺乏会诱导更强的T细胞活化，并证明SIRT5在调节CD4 ⁺的分化中起关键作用调节性T（Treg）细胞和T辅助1（Th1）细胞。免疫抑制性Treg细胞谱系和辅助性T细胞的炎性Th1亚型不平衡会导致结肠癌的发展。我们的结果揭示了SIRT5在T细胞活化和结肠直肠肿瘤发生中的调节作用。