微生物代謝産物に対するアストロサイトのマイクログリアル制御
Veit Rothhammer1, Davis M Borucki1, Emily C Tjon1
1Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nature
|May 18, 2018
まとめ
マイクログリアは,TGFαとVEGF-Bを介して,中枢神経系 (CNS) のアストロサイト活動を調節する. 食中の微生物とその代謝産物は 中枢神経系の炎症を抑制し 多発性硬化症の治療法となる可能性があります
科学分野:
- 神経科学
- 免疫学
- 微生物学
背景:
- マイクログリアとアストロサイトは,中枢神経系 (CNS) の炎症と神経変性における重要な細胞です.
- マイクログリアがアストロサイトの炎症促進および神経毒性を調節するメカニズムは完全に理解されていません.
研究 の 目的:
- 神経炎症の時にアストロサイトの活動を調節するマイクログリアル由来因子の役割を調査する.
- 微生物代謝産物のマイクログリアル-アストロサイト相互作用と中枢神経系炎症への影響を調査する.
主な方法:
- 多発性硬化症の実験的な自己免疫脳炎 (EAE) マウスモデルを使用した.
- マイクログリアとアストロサイトにおけるTGFαとVEGF-Bの発現と機能を分析した.
- 食中のトリプトファン代謝産物とアリル炭水化物受容体の役割を調査した.
主要な成果:
- マイクログリア由来のTGFαは,ErbB1シグナル伝達により,病原性アストロサイト活動とEAEの重症性を制限する.
- マイクログリアルVEGF-Bは,アストロサイトにおけるFLT- 1シグナル伝達を活性化することによってEAEを悪化させる.
- CD14+細胞におけるTGFαとVEGF-Bの発現は,多発性硬化症の病変段階と相関しています.
- 食中のトリプトファンの代謝物は,ミクログリアの活性化と天体細胞の転写プログラムを調節し,アリル炭水化物受容体を通して中枢神経の炎症を抑制する.
結論:
- TGFαとVEGF-Bは,中枢神経系の微小細胞のコントロールの重要なレギュレータとして特定されました.
- 微生物代謝物が神経炎症を抑制する 経路を発見した
- これらの発見は,多発性硬化症やその他の神経疾患の治療戦略の可能性を示唆しています.
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