Perazzio Aline S B, Oliveira José Salvador R, Figueiredo Vera L P, Chauffaille Maria de Lourdes L F
Division of Hematology, Federal University of São Paulo, São Paulo, SP, Brazil; Fleury Group, Research and Development, São Paulo, SP, Brazil.
Division of Hematology, Federal University of São Paulo, São Paulo, SP, Brazil; Division of Hematology, Hospital Santa Marcelina, São Paulo, SP, Brazil.
Leuk Res. 2017 Apr;55:6-17. doi: 10.1016/j.leukres.2017.01.008. Epub 2017 Jan 5.
Studies have demonstrated that abnormalities in interferon regulatory factor-1 (IRF-1) expression might develop myelodysplastic syndromes (MDS). IRF-1 was described as modulator of T regulatory (Treg) cells by suppressing Foxp3 on mice. We aimed to determine the role of Treg and IRF-1 in MDS. Thirty-eight MDS patients fulfilling WHO criteria and classified according to risk scores were evaluated at time 0 (T0) and after 12 months (T12) for: Treg suppression activity in coculture with T effector (Teff) cells; IRF-1 and Foxp3 genetic expression by qRT-PCR; IL-2, -4, -6, -10, -17, TNFα and IFNγ production by Cytometric Bead Array. No differences in Foxp3 expression (T0=0.06±0.06 vs T12=0.06±0.12, p=0.5), Treg number (T0=5.62±2.84×10 vs T12=4.87±2.62×10; p=0.3) and Teff percentage (T0=16.8±9.56% vs T12=13.1±6.3%; p=0.06) were observed on T12. Low risk MDS patients showed a higher number of Treg (5.2±2.6×10) versus high risk group (2.6±1.2×10, p=0.03). Treg suppression activity was impaired on T0 and T12.Cytokine production and IRF-1 expression were increased on T12. The correlation between IRF-1 and FoxP3 was negative (r=0.317, p=0.045) on T0. These results suggest a hyper activity of the immune system, probably secondary to Treg suppression activity impairment. This state may induce the loss of tolerance culminating in the proliferation of MDS clones.
研究表明，干扰素调节因子-1（IRF-1）表达异常可能会引发骨髓增生异常综合征（MDS）。在小鼠中，IRF-1通过抑制Foxp3被描述为调节性T（Treg）细胞的调节剂。我们旨在确定Treg和IRF-1在MDS中的作用。对38例符合WHO标准并根据风险评分分类的MDS患者在时间0（T0）和12个月后（T12）进行评估，评估内容包括：与效应T（Teff）细胞共培养时Treg的抑制活性；通过qRT-PCR检测IRF-1和Foxp3基因表达；通过细胞计数珠阵列检测IL-2、-4、-6、-10、-17、TNFα和IFNγ的产生。在T12时未观察到Foxp3表达（T0 = 0.06±0.06 vs T12 = 0.06±0.12，p = 0.5）、Treg数量（T0 = 5.62±2.84×10 vs T12 = 4.87±2.62×10；p = 0.3）和Teff百分比（T0 = 16.8±9.56% vs T12 = 13.1±6.3%；p = 0.06）的差异。低风险MDS患者的Treg数量（5.2±2.6×10）高于高风险组（2.6±1.2×10，p = 0.03）。T0和T12时Treg抑制活性受损。T12时细胞因子产生和IRF-1表达增加。T0时IRF-1与FoxP3之间的相关性为负（r = 0.317，p = 0.045）。这些结果表明免疫系统存在过度活跃，可能继发于Treg抑制活性受损。这种状态可能导致耐受性丧失，最终导致MDS克隆增殖。
