miR-106b-5p induces immune imbalance of Treg/Th17 in immune thrombocytopenic purpura through NR4A3/Foxp3 pathway
miR-106b-5p induces immune imbalance of Treg/Th17 in immune thrombocytopenic purpura through NR4A3/Foxp3 pathway
复制标题
miR-106b-5p通过NR4A3/Foxp3通路诱导免疫性血小板减少性紫癜Treg/Th17免疫失衡
DOI：
10.1080/15384101.2020.1746485
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发表时间：
2020-04
期刊：
影响因子：
4.3
通讯作者：
夏亚林
中科院分区：
文献类型：
--
作者：
李建琴;田健美;樊小如;王兆钺;凌婧;吴晓芳;杨飞韵;夏亚林
背景调节性T细胞（Treg）/辅助性T细胞17（Th 17）的免疫失衡参与了免疫性血小板减少性紫癜（ITP）的发生发展。miRNAs的失调在ITP的发展中是重要的。然而，miR-106 b-5 p在ITP中Treg/Th 17失衡中的作用仍然未知。材料与方法收集ITP患者和健康对照者外周血，分离CD 4 + T细胞。通过qRT-PCR、western blot或ELISA检测miR-106 b-5 p、核受体亚家族4 A组成员3（NR 4A 3）、叉头盒蛋白3（Foxp 3）、IL-17 A和TGF-β的表达。双荧光素酶报告基因检测miR-106 b-5 p对NR 4A 3的影响。结果与健康对照组相比，ITP患者外周血中miR-106 b-5 p表达升高，NR 4A 3表达降低。sh-NR 4A 3显著降低Foxp 3和TGF-β的表达，表明NR 4A 3可能通过Foxp 3调节Treg分化。此外，NR 4A 3被鉴定为miR-106 b-5 p的靶标，并且miR-106 b-5 p能够负调节NR 4A 3表达。此外，我们发现miR-106 b-5 p通过NR 4A 3诱导Treg/Th 17免疫失衡。体内实验显示，沉默miR-106 b-5 p促进Treg分化并增加血小板数量，表明ITP缓解。结论miR-106 b-5 p通过NR 4A 3/Foxp 3途径调节ITP患者Treg/Th 17免疫失衡。
ABSTRACT Background Immune imbalance of regulatory T cells (Treg)/T helper 17 cells (Th17) contributes to the development of immune thrombocytopenic purpura (ITP). The dysregulation of miRNAs is important in the development of ITP. However, the role of miR-106b-5p in Treg/Th17 imbalance remains unknown in ITP. Materials and methods Peripheral blood was collected from patients with ITP and healthy controls, and CD4 + T cells were further isolated. miR-106b-5p, nuclear receptor subfamily 4 group A member 3 (NR4A3), forkhead box protein 3 (Foxp3), IL-17A, and TGF-β expressions were detected by qRT-PCR, western blot, or ELISA. The effect of miR-106b-5p on NR4A3 was detected by dual-luciferase reporter gene assay. Results Compared with healthy controls, miR-106b-5p was elevated in peripheral blood of patients with ITP, and NR4A3 expression was decreased. sh-NR4A3 significantly decreased Foxp3 and TGF-β expressions, indicating that NR4A3 may regulate Treg differentiation via Foxp3. Additionally, NR4A3 was identified to be a target of miR-106b-5p, and miR-106b-5p was able to negatively modulate NR4A3 expression. Moreover, we found miR-106b-5p induced immune imbalance of Treg/Th17 through NR4A3. In vivo experiments revealed that silencing miR-106b-5p promoted Treg differentiation and increased the number of platelets, suggesting the relief of ITP. Conclusion miR-106b-5p regulated immune imbalance of Treg/Th17 in ITP through the NR4A3/Foxp3 pathway.
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影响因子：
158.5
作者：
Scully, M.;Cataland, S. R.;Zeldin, R. K.
通讯作者：
Zeldin, R. K.
影响因子：
3.1
作者：
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通讯作者：
Ya Wang;R. Huang;Chao-Yang Song;Haiyan Hu;Meixia Zhang
影响因子：
4
作者：
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通讯作者：
Han, Wei
影响因子：
5.4
作者：
Lee, Arim;Lim, Hui Xuan;Kim, Tae Sung
通讯作者：
Kim, Tae Sung
DOI：
10.1073/pnas.1605849113
发表时间：
2016-08-09
影响因子：
11.1
作者：
Pabbisetty, Sudheer K.;Rabacal, Whitney;Sebzda, Eric
通讯作者：
Sebzda, Eric