期刊
THROMBOSIS RESEARCH
卷 177, 期 -, 页码 70-78出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2019.03.005
关键词
Immune thrombocytopenia; miRNA; Treg cell; Th17 cell
资金
- National Natural Science Foundation of China [81800112, 81770133, 81470284, 81770114, 81500094, 81500095]
- Major Research plan of the National Natural Science Foundation of China [91442204]
- State Key Clinical Specialty of China for Blood Disorders and Tai Shan Scholar Foundation
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.
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