Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression.
Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression.
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DOI：
10.1371/journal.pone.0002705
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发表时间：
2008-07-16
期刊：
影响因子：
3.7
通讯作者：
Unutmaz D
中科院分区：
文献类型：
--
作者：
Wang R;Wan Q;Kozhaya L;Fujii H;Unutmaz D
调节性T（Treg）细胞控制免疫激活并维持耐受性。甲状腺激素如何介导其抑制功能尚不清楚。在这里，我们鉴定了一种称为GARP（或LRRC32）的细胞表面分子，其在T细胞内特异性表达于通过T细胞受体（TCR）激活的TcR中。GARP在人幼稚T（TN）细胞中的异位表达抑制TCR活化后的增殖和细胞因子分泌。值得注意的是，GARP在TN细胞中的过表达诱导了Treg主转录因子Foxp3的表达，并赋予它们部分抑制功能。GARP的胞外区而非胞浆区是这些功能所必需的。在人Treg细胞中沉默Foxp3降低了GARP的表达并减弱了它们的抑制功能。然而，当Foxp3在GARP过表达细胞中下调时，GARP功能不受影响，而在Foxp3过表达细胞中沉默GARP降低了它们的抑制活性。这些发现揭示了一种新的细胞表面分子介导的调节机制，与调节异常免疫反应的影响。
Regulatory T (Treg) cells control immune activation and maintain tolerance. How Tregs mediate their suppressive function is unclear. Here we identified a cell surface molecule, called GARP, (or LRRC32), which within T cells is specifically expressed in Tregs activated through the T cell receptor (TCR). Ectopic expression of GARP in human naïve T (TN) cells inhibited their proliferation and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in TN cells induced expression of Treg master transcription factor Foxp3 and endowed them with a partial suppressive function. The extracellular but not the cytoplasmic region of GARP, was necessary for these functions. Silencing Foxp3 in human Treg cells reduced expression of GARP and attenuated their suppressive function. However, GARP function was not affected when Foxp3 was downregulated in GARP-overexpressing cells, while silencing GARP in Foxp3-overexpressing cells reduced their suppressive activity. These findings reveal a novel cell surface molecule-mediated regulatory mechanism, with implications for modulating aberrant immune responses.
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