Aberrant expression of microRNA in CD4+ cells contributes to Th17/Treg imbalance in primary immune thrombocytopenia
Aberrant expression of microRNA in CD4+ cells contributes to Th17/Treg imbalance in primary immune thrombocytopenia
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CD4( )细胞中microRNA的异常表达导致原发性免疫性血小板减少症中Th17/Treg失衡
DOI：
10.1016/j.thromres.2019.03.005
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发表时间：
2019-05-01
影响因子：
7.5
通讯作者：
Feng, Qi
中科院分区：
文献类型：
--
作者：
Hua, Mingqiang;Li, Ju;Feng, Qi
简介：原发性免疫性血小板减少症（ITP）患者存在辅助性T细胞（Th 17）和调节性T细胞（Treg）失衡，但其机制尚不清楚。我们研究了辅助性T细胞或Treg细胞相关的microRNA（miRNAs）表达是否调节CD 4（+）T细胞中Th 17/Treg的比例。我们使用茎环引物和U6作为对照，使用RT-PCR检测miRNA表达。通过流式细胞术分析Th 17和Treg百分比。结果：ITP患者CD 4（+）细胞中miR-99 a的表达低于对照组，而miR-182 - 5 p和miR-183 - 5 p的表达高于对照组。此外，ITP患者中Treg百分比与miR-99 a表达呈正相关。我们发现Th 17百分比与miR-182- 5 p或miR-183- 5 p表达之间没有显著相关性。miR-183- 5 p表达与血小板计数呈负相关，而血小板计数与miR-99 a或miR-182- 5 p之间无显著差异。重症患者CD 4（+）T细胞中miR-183- 5 p的表达显著高于非重症患者。此外，下调miR-183- 5 p表达抑制了Th 17分化，而上调miR-99 a增加了ITP患者CD 4（+）细胞中检测到的TcR。结论：ITP患者CD 4+细胞中miR-99 a、miR-182- 5 p和miR-183- 5 p表达水平异常。miRNAs的异常表达可能导致ITP患者Th 17/Treg失衡，并可能代表一种新的治疗靶点。
Introduction: Imbalance of T helper 17 (Th17) cells and regulatory T (Treg) cells occurs in primary immune thrombocytopenia (ITP), but the mechanism remains unclear. We investigated whether expression of microRNAs (miRNAs) related to helper T or Treg cells regulate the Th17/Treg ratio in CD4(+) T cells.Materials and methods: Peripheral blood was obtained from 52 active ITP patients and 56 healthy controls. We detected miRNA expression using RT-PCR with stem-loop primers and U6 as control. Th17 and Treg percentages were analyzed by flow cytometry. CD4(+) cells were transfected with miRNA (miR-99a, miR-182-5p, miR-183-5p) mimics or inhibitors to investigate their function.Results: miR-99a expression in CD4(+) cells in ITP patients was lower than in controls, while expression of miR-182-5p and miR-183-5p were higher in ITP patients. Moreover, Treg percentage correlated positively with miR-99a expression in ITP patients. We found no significant correlation between Th17 percentage and miR-182-5p or miR-183-5p expression. miR-183-5p expression correlated negatively with platelet count, while we found no significant difference between platelet count and miR-99a or miR-182-5p. miR-183-5p expression in CD4(+) T cells from severe patients was significantly higher than in those from non-severe patients. Furthermore, down-regulating miR-183-5p expression repressed Th17 differentiation, while up-regulating miR-99a increased Tregs detected in CD4(+) cells from ITP patients. In addition, up-regulated miR-99a repressed mTOR and p-mTOR expression.Conclusions: miR-99a, miR-182-5p, and miR-183-5p expression levels in CD4(+) cells were abnormal in ITP patients. Aberrant expression of miRNAs may contribute to the Th17/Treg imbalance in ITP patients and may represent a novel therapeutic target.