Department of Hematology, General Hospital of Tianjin Medical University, Tianjin, China.
Department of Hematology, General Hospital of Tianjin Medical University, Tianjin, China,
Acta Haematol. 2019;142(3):142-148. doi: 10.1159/000497404. Epub 2019 May 29.
Recent studies have indicated that Sirt1 plays critical roles in the suppression of inflammation, T cell activation, and differentiation of hematopoietic progenitor cells. Severe aplastic anemia (SAA) is an immune-mediated disease that is characterized by elevated cytotoxic lymphocytes and type 1 cytokines. As a negative effector cytokine, interferon gamma (IFNγ) takes part in aplastic anemia through its inhibitory effect on hematopoiesis. In this study, we investigated the role of Sirt1 in the regulation of IFNγ in patients with SAA. A significant decrease in relative SIRT1 (p< 0.05) and increase in IFNG (p< 0.05) expression levels was observed in the sorted CD8+T cells of SAA patients compared to the controls. There was a significant negative correlation (r = -0.53, p < 0.05) between SIRT1 and IFNG expression in SAA patients. SRT3025, a Sirt1 activator, was shown to significantly reduce IFNγ (p < 0.01) and elevate Sirt1 (p < 0.05) expression in the CD8+T cells of SAA patients, and also showed a therapeutic role in an aplastic anemia mouse model. In conclusion, the defective Sirt1 may be correlated to the abnormal IFNγ expression in SAA patients, and activation of Sirt1 signaling may help improve the inflammatory status of SAA.
最近的研究表明，Sirt1 在抑制炎症、T 细胞激活和造血祖细胞分化方面发挥着关键作用。严重再生障碍性贫血（SAA）是一种免疫介导的疾病，其特征是细胞毒性淋巴细胞和 1 型细胞因子水平升高。作为一种负效细胞因子，干扰素 γ（IFNγ）通过对造血的抑制作用参与再生障碍性贫血的发生。在本研究中，我们研究了 Sirt1 在调节 SAA 患者 IFNγ 中的作用。与对照组相比，SAA 患者分选的 CD8+T 细胞中相对 SIRT1（p<0.05）和 IFNG（p<0.05）表达水平显著降低。SAA 患者中 SIRT1 和 IFNG 表达之间存在显著负相关（r=-0.53，p<0.05）。Sirt1 激活剂 SRT3025 可显著降低 SAA 患者 CD8+T 细胞中 IFNγ（p<0.01）和升高 Sirt1（p<0.05）的表达，并在再生障碍性贫血小鼠模型中显示出治疗作用。总之，Sirt1 的缺陷可能与 SAA 患者 IFNγ 表达异常有关，激活 Sirt1 信号通路可能有助于改善 SAA 的炎症状态。
