Foxp3 is a novel repressor of microglia activation

Abstract

Forkhead transcription factor3 (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 (Foxp3sf), 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-α and IL-1β 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-κB and modulates its transcriptional activities. These findings point to the importance of Foxp3 in NF-κB mediated inflammatory responses in microglia. © 2010 Wiley-Liss, Inc.