Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea; Department of Physiology, Bangladesh Agricultural University, Mymensingh, Bangladesh.
Eur J Immunol. 2013 Sep;43(9):2484-96. doi: 10.1002/eji.201243046. Epub 2013 Jul 1.
Early growth response gene 2 (Egr2), which encodes a zinc finger transcription factor, is rapidly and transiently induced in various cell types independently of de novo protein synthesis. Although a role for Egr2 is well established in T-cell development, Egr2 expression and its biological function in dendritic cells (DCs) have not yet been described. Here, we demonstrate Egr2 expression during DC development, and its role in DC-mediated immune responses. Egr2 is expressed in the later stage of DC development from BM precursor cells. Even at steady state, Egr2 is highly expressed in mouse splenic DCs. Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities. Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine. DC-mediated cytotoxic T lymphocyte (CTL) activation and antitumor immunity were significantly enhanced by Egr2-KD, and impaired by Egr2 overexpression in antigen-pulsed DC vaccines. These data suggest that Egr2 acts as an intrinsic negative regulator of DC immunogenicity and can be an attractive molecular target for DC vaccine development.
早期生长反应基因 2（Egr2），编码锌指转录因子，在各种细胞类型中独立于新蛋白质合成而快速和短暂地诱导。虽然 Egr2 在 T 细胞发育中具有重要作用，但 Egr2 在树突状细胞（DC）中的表达及其生物学功能尚未描述。在这里，我们证明了 Egr2 在 DC 发育过程中的表达及其在 DC 介导的免疫反应中的作用。Egr2 在来自 BM 前体细胞的 DC 发育的后期阶段表达。即使在稳定状态下，Egr2 在小鼠脾脏 DC 中也高度表达。Egr2 敲低（Egr2-KD）DC 显示出 MHC 类 I 和 II 以及共刺激分子的水平增加，并且增强了抗原摄取和迁移能力。此外，Egr2-KD 在 DC 发育过程中消除了 SOCS1 表达和信号转导和转录激活物 5（STAT5）的激活，可能导致 IL-12 表达和 DC 疫苗的 Th1 免疫原性增强。Egr2-KD 显著增强了 DC 介导的细胞毒性 T 淋巴细胞（CTL）激活和抗肿瘤免疫，而在抗原脉冲的 DC 疫苗中 Egr2 过表达则损害了这种作用。这些数据表明，Egr2 作为 DC 免疫原性的内在负调节剂起作用，并且可以成为 DC 疫苗开发的有吸引力的分子靶标。
