Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat, Egypt.
South Egypt Cancer Institute, Assiut University, Assuite, Egypt.
Mol Immunol. 2020 Aug;124:1-8. doi: 10.1016/j.molimm.2020.05.002. Epub 2020 May 30.
Regulatory T cells (Tregs) is one of the immunosuppressive subsets of CD4 T cells characterized by transcription factor forkhead box protein P3 (FOXP3) expression which are involved in tumor development and progression. Identification of the factors that influence Treg cell function is extremely important. Our current study aimed to evaluate the frequency of Treg cells, cytokine secretion and the expression of microRNAs (miRNAs) in pediatric acute lymphoblastic leukemia (ALL) patients. The frequency of CD3, CD4 and CD4CD25FOXP3 Treg was assessed by flow cytometry in 43 ALL patients versus 42 controls. Plasma levels of IL-10, transcription factor β (TGF-β), IL-6, IL-17, IL-23 and tumor necrosis factor (TNF-α) were measured by Enzyme-linked immunosorbent assay (ELISA). miR-21, miR-24, miR-26a, miR133b, miR-148a and miR-155 expression were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). A slight insignificant increase in Treg cells in ALL patients compared to controls was observed. There was a significant elevation in IL-10 (p < 0.05), IL-6 (p < 0.01), IL-23 (p < 0.05) and TNF-α (p < 0.01) in ALL patients compared with controls. Meanwhile, a significant reduction in TGF-β (p < 0.001) was recorded. A slight insignificant decrease in IL-17 in ALL patients was observed.ALL patients showed a significant increase in miR-21 (p < 0.05), miR-148a (p < 0.01), miR-24 (p < 0.05) and a significant reduction in miR-155 (p < 0.01). In conclusion, the slight change in Treg cells frequency and alteration in related cytokines could possibly involve in the pathogenesis of ALL. Dysregulated miRNAs, as a regulatory mechanism of epigenetics, might contribute to these observed results. Further researches are required to confirm our interesting findings.
调节性 T 细胞（Tregs）是 CD4 T 细胞的免疫抑制亚群之一，其特征在于转录因子叉头框蛋白 P3（FOXP3）的表达，它参与肿瘤的发生和发展。鉴定影响 Treg 细胞功能的因素非常重要。我们目前的研究旨在评估儿童急性淋巴细胞白血病（ALL）患者 Treg 细胞的频率、细胞因子分泌和 microRNAs（miRNAs）的表达。通过流式细胞术评估 43 例 ALL 患者和 42 例对照中 CD3、CD4 和 CD4CD25FOXP3 Treg 的频率。通过酶联免疫吸附试验（ELISA）测量血浆中白细胞介素-10（IL-10）、转录因子β（TGF-β）、白细胞介素-6（IL-6）、白细胞介素-17（IL-17）、白细胞介素-23（IL-23）和肿瘤坏死因子（TNF-α）的水平。使用实时定量聚合酶链反应（qRT-PCR）分析 miR-21、miR-24、miR-26a、miR133b、miR-148a 和 miR-155 的表达。与对照组相比，ALL 患者的 Treg 细胞略有增加，但无统计学意义。与对照组相比，ALL 患者的 IL-10（p<0.05）、IL-6（p<0.01）、IL-23（p<0.05）和 TNF-α（p<0.01）显著升高。同时，TGF-β（p<0.001）显著降低。ALL 患者的 IL-17 略有降低。ALL 患者的 miR-21（p<0.05）、miR-148a（p<0.01）、miR-24（p<0.05）显著增加，miR-155（p<0.01）显著降低。总之，Treg 细胞频率的轻微变化和相关细胞因子的改变可能参与 ALL 的发病机制。作为表观遗传调控机制的失调 miRNA 可能导致这些观察结果。需要进一步的研究来证实我们的有趣发现。
