title: CD200R/Foxp3-mediated signalling regulates microglial activation.
abstract: The heterogeneity of microglial functions have either beneficial or detrimental roles in specific physiological or pathological environments. However, the details of what transcriptional mechanisms induce microglia to take beneficial phenotypes remain unknown. Here, we report that Foxp3 is essential for beneficial outcome of the microglial response and depends upon signalling by the immunoglobulin CD200 through its receptor (CD200R). Foxp3 expression was up-regulated in microglia activated by excitotoxicity-induced hippocampal neuroinflammation. Suppression of CD200R prevented anti-inflammatory phenotype of microglia, but over-expression of Foxp3 enhanced it. Phosphorylation of STAT6, a downstream effector of CD200R, modulated transcription of Foxp3. Finally, CD200R/Foxp3-mediated signalling enhanced hippocampal neuronal viability and conferred a degree of neuroprotection, presumably by counteracting inducible nitric oxide synthase. We conclude that enhancement of Foxp3 through CD200R could be neuroprotective by targeting the microglia.
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.|Department of Neuroscience &Cell Biology, the University of Texas Medical Branch School of Medicine, Galveston, TX 77555, USA.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Yi
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.|Department of Anesthesiology, Yanbian University Hospital, Yanbian, 133000, China.
authors.forename: Enji
authors.initials: E
authors.lastname: Zhang
authors.affiliation: LES Corporation Inc., Gung-Dong 465-16, Yuseong-Gu Daejeon, 305-335, Republic of Korea.
authors.forename: Jwa-Jin
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Baek
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.
authors.forename: Nara
authors.initials: N
authors.lastname: Shin
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.|Department of Plastic Surgery, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
authors.forename: Sena
authors.initials: S
authors.lastname: Kim
authors.affiliation: School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, and Biomedical Sciences Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Physiology, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.affiliation: Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, USA.
authors.forename: Yonghyun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.
authors.forename: O-Yu
authors.initials: OY
authors.lastname: Kwon
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Plastic Surgery, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
authors.forename: Sang-Ha
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, Republic of Korea.|Department of Medical Science, Chungnam National University School of Medicine Daejeon, 301-747, Republic of Korea.
authors.forename: Dong Woon
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D002470:Cell Survival; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D007249:Inflammation; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; C492346:CD200 receptor, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; C494087:Stat3 protein, mouse; C494100:Stat6 protein, mouse; D049452:Green Fluorescent Proteins; D009569:Nitric Oxide; D007608:Kainic Acid; C042739:antigens, CD200