Roles of regulatory T cells in the pathogenesis of pediatric aplastic anemia
Roles of regulatory T cells in the pathogenesis of pediatric aplastic anemia
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调节性 T 细胞在小儿再生障碍性贫血发病机制中的作用
DOI：
10.1080/08880018.2019.1621968
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发表时间：
2019-07-06
影响因子：
1.7
通讯作者：
Chen, Chun
中科院分区：
文献类型：
--
作者：
Lin, Shaofen;Hou, Lele;Chen, Chun
摘要 儿童再生障碍性贫血（AA）的发病机制尚不清楚。本研究旨在探讨儿科 AA 中调节性 T 细胞 (Treg) 的比例和功能的变化。分别通过流式细胞术、逆转录PCR和酶联免疫吸附测定测定Treg的比例、转录因子的mRNA水平和细胞因子的浓度。 Tregs 与效应 T 细胞 (Teff) 共培养，以评估 Tregs 的功能。动态监测儿科 AA 免疫抑制治疗 (IST) 后的 Tregs 比例。与对照组相比，未治疗AA组外周血和骨髓淋巴细胞中Treg细胞的比例较低（分别为1.31%±0.73% vs. 3.16%±0.92%、1.49%±0.81% vs. 3.06%±0.82%，p<0.001）。 AA组中FOXP3和STAT3的mRNA水平较低(p = 0.014；p < 0.001)。然而，T-BET 的 mRNA 水平在各组之间没有显着差异。 AA组中干扰素-γ和白介素-17的浓度较高（p = 0.004；p = 0.003），而TGF-β的浓度降低（p = 0.044）。 AA组中Tregs的免疫抑制功能受损。 IST后，Tregs的比例明显低于对照组。无反应组诊断时Tregs的比例低于有反应组，但差异不显着。在诊断儿童 AA 时，Treg 水平显着下降且功能受损。然而，在 AA 决议中，Tregs 没有显着变化。
Abstract The pathogenesis of aplastic anemia (AA) in children is not clear. This study was conducted to investigate the changes in the proportion and function of regulatory T cells (Tregs) in pediatric AA. The proportion of Tregs, mRNA levels of transcription factors, and concentrations of cytokines were measured by flow cytometry, reverse transcription-PCR, and enzyme-linked immunosorbent assay, respectively. Tregs were co-cultured with effector T cells (Teff) to evaluate the function of Tregs. The proportion of Tregs after immunosuppressive therapy (IST) in pediatric AA was monitored dynamically. Compared to the control, the proportions of Tregs in peripheral blood and bone marrow lymphocytes of the untreated AA group were lower (1.31% ± 0.73% vs. 3.16% ± 0.92%, 1.49% ± 0.81% vs. 3.06% ± 0.82%, respectively, p < 0.001). The mRNA levels of FOXP3 and STAT3 in the AA group were lower (p = 0.014; p < 0.001). However, the mRNA levels of T-BET did not significantly differ between groups. The concentration of interferon-γ and interleukin-17 in the AA group were higher (p = 0.004; p = 0.003), whereas the concentration of TGF-β decreased (p = 0.044). The immunosuppressive function of Tregs was impaired in the AA group. After IST, the proportion of Tregs was significantly lower than that in the control. The proportion of Tregs at the time of diagnosis in the nonresponsive group was lower than that in the responsive group, but the difference was not significant. Treg levels were significantly decreased and were functionally impaired at the time of diagnosis of pediatric AA. However, there was no significant change in Tregs at the resolution of AA.