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鉴定一种调节性T细胞特异性细胞表面分子，该分子介导抑制性信号并诱导Foxp3表达。

Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression.

作者信息

Wang Rui, Wan Qi, Kozhaya Lina, Fujii Hodaka, Unutmaz Derya

机构信息

Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.

出版信息

PLoS One. 2008 Jul 16;3(7):e2705. doi: 10.1371/journal.pone.0002705.

DOI:10.1371/journal.pone.0002705
PMID:18628982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2442191/
Abstract

Regulatory T (T(reg)) cells control immune activation and maintain tolerance. How T(regs) 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 T(regs) activated through the T cell receptor (TCR). Ectopic expression of GARP in human naïve T (T(N)) cells inhibited their proliferation and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in T(N) cells induced expression of T(reg) 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 T(reg) 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.

摘要

调节性T（T(reg)）细胞控制免疫激活并维持免疫耐受。T(regs)如何介导其抑制功能尚不清楚。在此，我们鉴定出一种细胞表面分子，称为GARP（或LRRC32），其在T细胞中特异性表达于通过T细胞受体（TCR）激活的T(regs)中。GARP在人初始T（T(N)）细胞中的异位表达抑制了它们在TCR激活后的增殖和细胞因子分泌。值得注意的是，GARP在T(N)细胞中的过表达诱导了T(reg)主转录因子Foxp3的表达，并赋予它们部分抑制功能。GARP的细胞外而非细胞质区域对这些功能是必需的。在人T(reg)细胞中沉默Foxp3会降低GARP的表达并减弱其抑制功能。然而，当在过表达GARP的细胞中下调Foxp3时，GARP的功能不受影响，而在过表达Foxp3的细胞中沉默GARP会降低其抑制活性。这些发现揭示了一种新的细胞表面分子介导的调节机制，对调节异常免疫反应具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/370f68358737/pone.0002705.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/4917182e6688/pone.0002705.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/65f807c83d4d/pone.0002705.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/031423ecc39a/pone.0002705.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/7c2d64483f09/pone.0002705.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/370f68358737/pone.0002705.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/4917182e6688/pone.0002705.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/65f807c83d4d/pone.0002705.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/031423ecc39a/pone.0002705.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/7c2d64483f09/pone.0002705.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aef/2442191/370f68358737/pone.0002705.g005.jpg

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