Dysregulated miR34a/diacylglycerol kinase ζ interaction enhances T-cell activation in acquired aplastic anemia
Dysregulated miR34a/diacylglycerol kinase ζ interaction enhances T-cell activation in acquired aplastic anemia
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DOI：
10.18632/oncotarget.14046
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Jun Peng
中科院分区：
文献类型：
--
作者：
Yuan-xin Sun;Hui Li;Qi Feng;Xin Li;Ying-yi Yu;Li-wei Zhou;Yan Gao;Guosheng Li;Juan Ren;Chun-hong Ma;Cheng-jiang Gao;Jun Peng
Acquired aplastic anemia is an idiopathic paradigm of human bone marrow.failure syndrome, which involves active destruction of hematopoietic stem cells and.progenitors by cytotoxic T cells in the bone marrow. Aberrant expression of microRNAs.in T cells has been shown to lead to development of certain autoimmune diseases..In the present study, we performed a microarray analysis of miRNA expression in.bone marrow CD3+ T cells from patients with aplastic anemia and healthy controls..Overexpression of miR34a and underexpression of its target gene diacylglycerol.kinase (DGK) ζ in bone marrow mononuclear cells were validated in 41 patients and.associated with the severity of aplastic anemia. Further, the level of miR34a was.higher in naïve T cells from patients than from controls. The role of miR34a and DGKζ.in aplastic anemia was investigated in a murine model of immune-mediated bone.marrow failure using miR34a-/- mice. After T-cell receptor stimulation in vitro, lymph.node T cells from miR34a-/- mice demonstrated reduced activation and proliferation.accompanied with a less profound down-regulation of DGKζ expression and decreased.ERK phosphorylation compared to those from wild-type C57BL6 control mice. Infusion.of 5 × 106 miR34a-/- lymph node T cells into sublethally irradiated CB6F1 recipients.led to increased Lin-Sca1+CD117+ cells and less vigorous expansion of CD8+ T cells.than injection of same number of wild-type lymph node cells. Our study demonstrates.that the miR34a/DGKζ dysregulation enhances T-cell activation in aplastic anemia.and targeting miR34a may represent a novel molecular therapeutic approach for.patients with aplastic anemia.
