Foxp3 is a novel repressor of microglia activation.
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.
Chung
Hwan-Suck
HS
Department of Physiology, College of Oriental Medicine, Kyung Hee University, #1 Hoeki-Dong, Dongdaemoon-gu, Seoul, Republic of Korea.
Lee
Jun-Ho
JH
Kim
Hyunseong
H
Lee
Hyo-Jung
HJ
Kim
Sung-Hoon
SH
Kwon
Ho-Keun
HK
Im
Sin-Hyeog
SH
Bae
Hyunsu
H
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002452:Cell Count; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000276:immunology / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology* / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide