Lu Li-Fan, Gavin Marc A, Rasmussen Jeffrey P, Rudensky Alexander Y
Department of Immunology, University of Washington, Seattle, WA 98195-7650, USA.
Mol Cell Biol. 2007 Dec;27(23):8065-72. doi: 10.1128/MCB.01075-07. Epub 2007 Sep 24.
Global analyses of gene expression in regulatory T (Treg) cells, whose development is critically dependent upon the transcription factor Foxp3, have provided many clues as to the molecular mechanisms these cells employ to control immune responses and establish immune tolerance. Through these studies, G protein-coupled receptor 83 (GPR83) was found to be expressed at high levels in Treg-cell populations. However, its function remained unclear. Recently, it has been suggested that GPR83 is involved in the induction of Foxp3 expression in the peripheral nonregulatory Foxp3- CD4 T cells. To examine a role for GPR83 in Treg-cell biology, we generated and characterized GPR83-deficient mice. We have shown that GPR83 abolition does not result in measurable pathology or changes in the numbers or function of Foxp3+ Treg cells. Furthermore, while in vitro analysis suggested a potential involvement of GPR83 in transforming growth factor beta-dependent Foxp3 induction, there was no difference in the ability of nonregulatory GPR83-deficient and nondeficient Foxp3- T cells to acquire Foxp3 expression in vivo. Collectively, our results demonstrate that GPR83 is dispensable for Treg-cell development and function.
调节性T（Treg）细胞的发育严重依赖转录因子Foxp3，对其基因表达的全局分析为这些细胞用于控制免疫反应和建立免疫耐受的分子机制提供了许多线索。通过这些研究，发现G蛋白偶联受体83（GPR83）在Treg细胞群体中高水平表达。然而，其功能仍不清楚。最近，有人提出GPR83参与外周非调节性Foxp3-CD4 T细胞中Foxp3表达的诱导。为了研究GPR83在Treg细胞生物学中的作用，我们构建并鉴定了GPR83缺陷小鼠。我们已经表明，GPR83的缺失不会导致可测量的病理变化，也不会导致Foxp3+ Treg细胞数量或功能的改变。此外，虽然体外分析表明GPR83可能参与转化生长因子β依赖性Foxp3诱导，但在体内，非调节性GPR83缺陷和非缺陷的Foxp3-T细胞获得Foxp3表达的能力没有差异。总体而言，我们的结果表明GPR83对于Treg细胞的发育和功能是可有可无的。
