Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses.
Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses.
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DOI：
10.1016/j.cell.2010.08.012
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发表时间：
2010-09-17
期刊：
影响因子：
64.5
通讯作者：
Rudensky AY
中科院分区：
文献类型：
--
作者：
Lu LF;Boldin MP;Chaudhry A;Lin LL;Taganov KD;Hanada T;Yoshimura A;Baltimore D;Rudensky AY
Foxp3+调节性T （Treg）细胞通过限制不同类型的炎症反应来维持免疫稳态。在这里，我们报告了在Treg细胞中普遍表达的mirna之一miR-146a对其抑制功能至关重要。Treg细胞中miR-146a的缺乏导致免疫耐受的破坏，表现为多种器官中致命的ifn γ依赖性免疫介导病变。这可能是由于miR146a的直接靶标信号换能器和激活因子转录1 （Stat1）的表达和激活增强所致。同样，在选择性消融SOCS1 （IFNγ受体下游Stat1磷酸化的关键负调节因子）的Treg细胞中，Stat1激活的增加与类似的th1介导的病理有关。我们的研究结果表明，Treg抑制因子功能的特定方面由单个miRNA控制，Stat1激活的最佳范围对于Treg介导的Th1反应和相关自身免疫的控制很重要。
Foxp3+ regulatory T (Treg) cells maintain immune homeostasis by limiting different types of inflammatory responses. Here, we report that miR-146a, one of the miRNAs prevalently expressed in Treg cells, is critical for their suppressor function. The deficiency of miR-146a in Treg cells resulted in a breakdown of immunological tolerance manifested in a fatal IFNγ-dependent immune-mediated lesions in a variety of organs. This was likely due to augmented expression and activation of signal transducer and activator transcription 1 (Stat1), a direct target of miR146a. Likewise, heightened Stat1 activation in Treg cells subjected to a selective ablation of SOCS1, a key negative regulator of Stat1 phosphorylation downstream of IFNγ receptor, was associated with analogous Th1-mediated pathology. Our results suggest that specific aspects of Treg suppressor function are controlled by a single miRNA and that an optimal range of Stat1 activation is important for Treg-mediated control of Th1 responses and associated autoimmunity.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
DOI：
10.1084/jem.20061692
发表时间：
2006-10-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cobb BS;Hertweck A;Smith J;O'Connor E;Graf D;Cook T;Smale ST;Sakaguchi S;Livesey FJ;Fisher AG;Merkenschlager M
通讯作者：
Merkenschlager M
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
5.4
作者：
Cameron, Jennifer E.;Yin, Qinyan;Flemington, Erik K.
通讯作者：
Flemington, Erik K.