Sirt1 in the Regulation of Interferon Gamma in Severe Aplastic Anemia.

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.