食中のアミノ酸からシンビオントによって作られる宿主免疫調節性脂質
Sungwhan F Oh1,2, T Praveena3, Heebum Song4
1Department of Immunology, Blavatnik Institute of Harvard Medical School, Boston, MA, USA. soh2@bwh.harvard.edu.
Nature
|November 11, 2021
まとめ
Bacteroides fragilisのアルファ-ガラクソシルセラミド (BfaGCs) のような微生物から派生した分子は腸の免疫を調節する. 特定の分岐構造は,自然キラーT細胞の活性化と免疫の発達に不可欠です.
科学分野:
- 免疫学
- 微生物学
- 生物化学
背景:
- シンビオティックな微生物群の分子は腸の免疫成熟に不可欠です
- 宿主-微生物群の免疫相互作用を制御する分子機構は,まだ十分に理解されていません.
研究 の 目的:
- Bacteroides fragilisのアルファガラクソシルセラミド (BfaGCs) の構造特有の免疫調節活性について調査する.
- 自然キラーT細胞の反応を調節するBfaGCの分子メカニズムを解明する.
主な方法:
- 標的型脂質分析と合成アプローチ
- 分岐鎖アミノ酸代謝を欠いた Bacteroides fragilis ノックアウト株を使用した.
- CD1d-BfaGC-NKT細胞受容体複合体の共結晶構造と親和分析を行った.
主要な成果:
- 分岐鎖アミノ酸代謝が低下したB. fragilisは,分岐が減少したBfaGCを生成した.
- 変異株でコロニー化されたマウスは結腸NKT細胞の調節が低下した.
- BfaGCのスフィンガニン鎖の分岐はNKT細胞の活性化と下流の免疫遺伝子発現を決定する.
結論:
- BfaGCsはCD1d受限リガンドとして作用し,免疫調節を媒介する.
- BfaGCの構造的分岐は,その免疫調節機能に不可欠である.
- この研究は,エンドバイオティックメタボライトと宿主の免疫系相互作用の分子パラダイムを示しています.
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