Foxp3 对 MHC Ⅰ类分子表达的调控及其对调节性 T 细胞功能的影响。
Regulation of MHC class I expression by Foxp3 and its effect on regulatory T cell function.
机构信息
Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
出版信息
J Immunol. 2014 Mar 15;192(6):2892-903. doi: 10.4049/jimmunol.1302847. Epub 2014 Feb 12.
Expression of MHC class I molecules, which provide immune surveillance against intracellular pathogens, is higher on lymphoid cells than on any other cell types. In T cells, this is a result of activation of class I transcription by the T cell enhanceosome consisting of Runx1, CBFβ, and LEF1. We now report that MHC class I transcription in T cells also is enhanced by Foxp3, resulting in higher levels of class I in CD4(+)CD25(+) T regulatory cells than in conventional CD4(+)CD25(-) T cells. Interestingly, the effect of Foxp3 regulation of MHC class I transcription is cell type specific: Foxp3 increases MHC class I expression in T cells but represses it in epithelial tumor cells. In both cell types, Foxp3 targets the upstream IFN response element and downstream core promoter of the class I gene. Importantly, expression of MHC class I contributes to the function of CD4(+)CD25(+) T regulatory cells by enhancing immune suppression, both in in vitro and in vivo. These findings identify MHC class I genes as direct targets of Foxp3 whose expression augments regulatory T cell function.
MHC I 类分子的表达提供了针对细胞内病原体的免疫监视，其在淋巴细胞上的表达高于任何其他细胞类型。在 T 细胞中，这是由 Runx1、CBFβ 和 LEF1 组成的 T 细胞增强子激活 I 类转录的结果。我们现在报告称，MHC I 类转录在 T 细胞中也被 Foxp3 增强，导致 CD4+CD25+T 调节细胞中 I 类的水平高于传统的 CD4+CD25-T 细胞。有趣的是，Foxp3 对 MHC I 类转录的调节作用具有细胞类型特异性：Foxp3 在 T 细胞中增加 MHC I 类的表达，但在上皮肿瘤细胞中抑制其表达。在这两种细胞类型中，Foxp3 靶向 I 类基因的上游 IFN 反应元件和下游核心启动子。重要的是，MHC I 类的表达通过增强免疫抑制作用，有助于 CD4+CD25+T 调节细胞的功能，无论是在体外还是体内。这些发现确定了 MHC I 类基因是 Foxp3 的直接靶标，其表达增强了调节性 T 细胞的功能。
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