コンメンサル微生物由来ブチラートは,大腸の調節性T細胞の微分化を誘発する
Yukihiro Furusawa1, Yuuki Obata2, Shinji Fukuda3
11] RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa 230-0045, Japan [2] The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan [3].
Nature
|November 15, 2013
まとめ
クロストリディアのような腸内微生物は,免疫耐性を促進する. 発酵産物である微生物ブチラートは,腸内炎症を抑制し,免疫ホメオスタシスを維持するために不可欠な腸内調節性T細胞 (Treg) を誘発します.
科学分野:
- 免疫学 免疫学とは
- 微生物学 微生物学とは
- 胃腸内科 胃腸内科
背景:
- 腸内共生微生物は,宿主の粘膜の免疫系に大きな影響を与える.
- 調節性T細胞 (Treg) は,クロストリディアのような微生物によって誘発され,腸内炎症とアレルギー反応の制御に不可欠です.
- 共同微生物が結腸のTreg細胞を誘発する正確な分子機構は,ほとんど不明のままである.
研究 の 目的:
- 腸内微生物が結腸のTreg細胞を誘発する分子メカニズムを調査する.
- 大腸のTreg細胞の分化に関与する特定の微生物代謝物を特定する.
- 腸内炎症の管理における同定された代謝産物の治療的可能性を調査する.
主な方法:
- 腸内光の内容のNMRベースのメタボローム分析を比較する.
- Tレグ細胞の分化を評価するインビトロおよびインビボ実験.
- CD4(+) CD45RB(hi) T細胞を用いてマウス (Rag1(-/-)) の大腸炎モデルを誘導する.
- Foxp3の位置におけるヒストンの改変 (アセチル化) の分析.
主要な成果:
- 短鎖脂肪酸 (SCFA) のルミナル濃度は,結腸のTreg細胞数と正に相関しています.
- 重要なSCFAであるブチラートは,腸内Treg細胞の微分化の強力な誘導体として,in vitroとin vivoの両方で特定されました.
- ブチラート治療は,マウスモデルでの大腸炎の発症を改善しました.
- ブチラートは,Foxp3ロカス調節領域におけるヒストンH3アセチル化を強化し,Treg細胞誘導のメカニズムを示唆した.
結論:
- 微生物由来ブチラートは,大腸のTreg細胞の分化を誘発する重要な要因です.
- ブチラートは,Treg細胞誘導による腸内免疫的ホメオスタシスの維持に重要な役割を果たします.
- これらの発見は,宿主-微生物の相互作用と,炎症性腸疾患に対する潜在的な治療戦略に関する新しい洞察を提供します.
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