foxp3 is a novel repressor of microglia activation forkhead transcription factor 3 foxp3 is critical for generating cd4cd25 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 mcp1 cxcl10 and ros upon liposaccharide treatment than the wild type while tnfalpha and il1 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 nfkappab and modulates its transcriptional activities these findings point to the importance of foxp3 in nfkappab mediated inflammatory responses in microglia