Department of Physiology, College of Oriental Medicine, Kyung Hee University, #1 Hoeki-Dong, Dongdaemoon-gu, Seoul, Republic of Korea.
Glia. 2010 Aug;58(10):1247-56. doi: 10.1002/glia.21006.
Forkhead transcription factor 3 (Foxp3) is critical for generating CD4(+)CD25(+) regulatory T cells. However, its role in microglia has not been identified. Here, we show that Foxp3 is expressed in microglia and is upregulated upon activation. In Foxp3 mutant mice (Foxp3(sf)), microglia release higher levels of inflammatory cytokines and mediators such as NO, MCP-1, CXCL10, and ROS upon liposaccharide treatment than the wild type, while TNF-alpha and IL-1 beta were not significantly different between wild and mutant microglial cells. In addition, Foxp3 silencing enhances inflammatory responses, suggesting that the major role of Foxp3 in microglia is that of a repressor of activation. Similarly, Foxp3 overexpression reduces inflammatory responses in microglia. We also demonstrate that Foxp3 interacts directly with NF-kappaB and modulates its transcriptional activities. These findings point to the importance of Foxp3 in NF-kappaB mediated inflammatory responses in microglia.
叉头框转录因子 3（Foxp3）对于生成 CD4(+)CD25(+)调节性 T 细胞至关重要。然而，其在小胶质细胞中的作用尚未确定。在这里，我们表明 Foxp3 在小胶质细胞中表达，并在激活时上调。在 Foxp3 突变小鼠（Foxp3(sf)）中，小胶质细胞在脂多糖处理后释放更高水平的炎症细胞因子和介质，如 NO、MCP-1、CXCL10 和 ROS，而 TNF-alpha 和 IL-1 beta 在野生型和突变型小胶质细胞之间没有显著差异。此外，Foxp3 沉默增强了炎症反应，表明 Foxp3 在小胶质细胞中的主要作用是作为激活的抑制剂。同样，Foxp3 的过表达减少了小胶质细胞中的炎症反应。我们还证明 Foxp3 与 NF-kappaB 直接相互作用并调节其转录活性。这些发现表明 Foxp3 在 NF-kappaB 介导的小胶质细胞炎症反应中的重要性。
