SIRT5 Contributes to Colorectal Cancer Growth by Regulating T Cell Activity
SIRT5 Contributes to Colorectal Cancer Growth by Regulating T Cell Activity
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SIRT5 通过调节 T 细胞活性促进结直肠癌生长
DOI：
10.1155/2020/3792409
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发表时间：
2020-09-01
影响因子：
4.1
通讯作者：
Yu, Hongxiu
中科院分区：
文献类型：
--
作者：
Wang, Ke;Hu, Zuojian;Yu, Hongxiu
在过去的几年中，SIRT 5在代谢调节中引起了相当大的关注。然而，SIRT 5通过调节肿瘤微环境在肿瘤发生中的功能知之甚少。在这项工作中，我们发现Sirt 5基因敲除小鼠对AOM和DSS诱导的结肠炎相关的结直肠肿瘤发生具有抗性，并且其肿瘤微环境中的IFN-γ水平较高。此外，蛋白质组和网络分析显示SIRT 5在T细胞受体信号通路中很重要。此外，我们确定了Sirt 5的缺陷诱导更强的T细胞活化，并证明SIRT 5在调节CD 4+调节性T（Treg）细胞和T辅助性1（Th 1）细胞的分化中起关键作用。免疫抑制性Treg细胞和辅助性T细胞的炎性Th 1亚群的谱系失衡导致结肠癌的发展。我们的研究结果揭示了SIRT 5在T细胞活化和结直肠肿瘤发生中的调节作用。
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.