CD200R/Foxp3-mediated signalling regulates microglial activation

Min Hee Yi; Enji Zhang; Jwa Jin Kim; Hyunjung Baek; Nara Shin; Sena Kim; Sang Ryong Kim; Hang Rae Kim; Sung Joong Lee; Jin Bong Park; Yonghyun Kim; O. Yu Kwon; Young Ho Lee; Sang Ha Oh; Dong Woon Kim

doi:10.1038/srep34901

CD200R/Foxp3-mediated signalling regulates microglial activation

Min Hee Yi, Enji Zhang, Jwa Jin Kim, Hyunjung Baek, Nara Shin, Sena Kim, Sang Ryong Kim, Hang Rae Kim, Sung Joong Lee, Jin Bong Park, Yonghyun Kim, O. Yu Kwon, Young Ho Lee, Sang Ha Oh, Dong Woon Kim

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18 Scopus citations

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.

Original language	English
Article number	34901
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep34901
State	Published - 12 Oct 2016

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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.",

author = "Yi, {Min Hee} and Enji Zhang and Kim, {Jwa Jin} and Hyunjung Baek and Nara Shin and Sena Kim and Kim, {Sang Ryong} and Kim, {Hang Rae} and Lee, {Sung Joong} and Park, {Jin Bong} and Yonghyun Kim and Kwon, {O. Yu} and Lee, {Young Ho} and Oh, {Sang Ha} and Kim, {Dong Woon}",

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = oct,

day = "12",

doi = "10.1038/srep34901",

language = "English",

volume = "6",

journal = "Scientific Reports",

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T1 - CD200R/Foxp3-mediated signalling regulates microglial activation

AU - Yi, Min Hee

AU - Zhang, Enji

AU - Kim, Jwa Jin

AU - Baek, Hyunjung

AU - Shin, Nara

AU - Kim, Sena

AU - Kim, Sang Ryong

AU - Kim, Hang Rae

AU - Lee, Sung Joong

AU - Park, Jin Bong

AU - Kim, Yonghyun

AU - Kwon, O. Yu

AU - Lee, Young Ho

AU - Oh, Sang Ha

AU - Kim, Dong Woon

PY - 2016/10/12

Y1 - 2016/10/12

N2 - 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.

AB - 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.

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SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 34901

ER -

CD200R/Foxp3-mediated signalling regulates microglial activation

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