The Role of the Basic Helix-Loop-Helix Transcription Factor Dec1 in the Regulatory T Cells
The Role of the Basic Helix-Loop-Helix Transcription Factor Dec1 in the Regulatory T Cells
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DOI：
10.4049/jimmunol.1001381
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发表时间：
2010-12-15
影响因子：
4.4
通讯作者：
Honda, Hiroaki
中科院分区：
文献类型：
--
作者：
Miyazaki, Kazuko;Miyazaki, Masaki;Honda, Hiroaki
天然存在的调节性T（Treg）细胞在维持免疫稳态和抑制自发性炎症反应的发展中起核心作用。然而，Treg稳态的潜在机制仍不完全清楚。特别值得注意的是，IL-2 Ra（CD 25）对于Treg细胞的稳态和预防淋巴增生性自身免疫性疾病至关重要。在本文中，我们报告，基本的螺旋-环-螺旋转录因子Dec 1参与调节性T细胞的稳态，并在其生存或扩大过继转移到淋巴细胞减少的收件人后发挥作用。因此，它对于抑制效应T细胞介导的炎症反应至关重要。Dec 1的增强表达上调了胸腺细胞发育过程中的CD 25表达，并增加了外周Treg细胞的数量。Dec 1结合转录因子Runx 1并与Runx 1共定位于Treg细胞中。具体来说，我们证明，在Treg细胞的Dec 1/Runx 1复合物结合到调控元件中存在的IL-2 R α基因座。总的来说，这些数据显示了Dec 1在Treg细胞中的作用机制。免疫学杂志，2010，185：7330-7339。
Naturally occurring regulatory T (Treg) cells play a central role in the maintenance of immune homeostasis and in restraining the development of spontaneous inflammatory responses. However, the underlying mechanisms of Treg homeostasis remain incompletely understood. Of particular note, the IL-2R alpha (CD25) is crucial for the homeostasis of Treg cells and the prevention of lymphoproliferative autoimmune disease. In this paper, we report that the basic helix-loop-helix transcription factor Dec1 is involved in the homeostasis of Treg cells and plays a role in their survival or expansion after adoptive transfer to lymphopenic recipients. Hence, it is crucial for the suppression of effector T cell-mediated inflammatory responses. Enforced expression of Dec1 upregulates CD25 expression during thymocyte development and increases the number of Treg cells in the periphery. Dec1 binds the transcription factor Runx1 and colocalizes with Runx1 in Treg cells. Specifically, we demonstrate that in Treg cells the Dec1/Runx1 complex binds to regulatory elements present in the Il-2r alpha locus. Collectively, these data show how Dec1 mechanistically acts in Treg cells. The Journal of Immunology, 2010, 185: 7330-7339.