MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis
MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis
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MiR-125a 的目标是稳定 Treg 介导的免疫稳态的效应器程序。
DOI：
10.1038/ncomms8096
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发表时间：
2015-05-01
影响因子：
16.6
通讯作者：
Shen, Nan
中科院分区：
文献类型：
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作者：
Pan, Wen;Zhu, Shu;Shen, Nan
虽然不同的自身免疫性疾病显示离散的临床特征，但有共同的分子途径密切相关。我们发现miR-125 a在包括系统性红斑狼疮和克罗恩病在内的人类自身免疫性疾病以及相关的自身免疫性小鼠模型的外周CD 4（+）T细胞中下调。miR-125 a稳定Treg细胞的定型和免疫调节能力。在miR-125 a缺陷小鼠中，平衡似乎从免疫抑制转向炎症，并导致更严重的结肠炎和实验性自身免疫性脑脊髓炎（EAE）发病机制。全基因组靶点分析显示，miR-125 a抑制了几种效应T细胞因子，包括Stat 3，Ifng和Il 13。使用化学合成的miR-125 a类似物，我们显示出在EAE模型中重新编程免疫稳态的潜力。这些发现指出miR-125 a是通过稳定Treg介导的免疫稳态来控制自身免疫性疾病的关键因素。
Although different autoimmune diseases show discrete clinical features, there are common molecular pathways intimately involved. Here we show that miR-125a is downregulated in peripheral CD4(+) T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn's disease, and relevant autoimmune mouse models. miR-125a stabilizes both the commitment and immunoregulatory capacity of Treg cells. In miR-125a-deficient mice, the balance appears to shift from immune suppression to inflammation, and results in more severe pathogenesis of colitis and experimental autoimmune encephalomyelitis (EAE). The genome-wide target analysis reveals that miR-125a suppresses several effector T-cell factors including Stat3, Ifng and Il13. Using a chemically synthesized miR-125a analogue, we show potential to re-programme the immune homeostasis in EAE models. These findings point to miR-125a as a critical factor that controls autoimmune diseases by stabilizing Treg-mediated immune homeostasis.