生まれつきの免疫と腸内微生物群が,第1型糖尿病の発症に及ぼす影響
Li Wen1, Ruth E Ley, Pavel Yu Volchkov
1Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|September 23, 2008
まとめ
生まれながらの免疫系である.
科学分野:
- 免疫学 免疫学とは
- 微生物学 微生物学とは
- エンドクリノロジー エンドクリノロジー
背景:
- 1型糖尿病 (T1D) は,インスリン生成ベータ細胞の破壊によって特徴づけられる自己免疫疾患です.
- T1Dの発生率の増加は,微生物群を含む環境要因が病原性に影響することを示唆しています.
- 非肥満糖尿病 (NOD) のマウスモデルは,T1Dを自発的に発症し,環境微生物の調節に敏感である.
研究 の 目的:
- T1D発症におけるMyD88依存の先天性免疫信号伝達の役割を調査する.
- NODマウスにおけるT1D病原性に対するコンメンサル腸内微生物群の影響を決定する.
- T1Dの予防のための微生物介入の可能性を調査する.
主な方法:
- MyD88欠乏のNODマウス (特定の病原体と細菌の両方) を利用しました.
- 異なる微生物環境におけるT1Dの発生率と進行を評価した.
- 16S rRNA配列解析を用いて腸内微生物の組成を分析した.
- 微生物の植民と糞便の微生物群移植の効果を調査した.
主要な成果:
- MyD88タンパク質を欠いた特定の病原体のないNODマウスはT1Dを発症しなかった.
- 細菌のないMyD88陰性NODマウスは糖尿病を発症し,共生微生物への依存を示した.
- MyD88欠乏のドナーから定義された微生物コンソーシアムまたは微生物群とのコロニー化により,細菌のないNODマウスのT1Dが弱まった.
- MyD88欠乏症は腸内微生物群の組成を変化させた.
結論:
- MyD88経由で腸内微生物と先天的な免疫系との相互作用は,T1D発症に不可欠です.
- コンメンサル腸内微生物群は,T1Dの感受性に影響を与える重要な表遺伝子因子として作用します.
- 腸内微生物群と先天的な免疫経路をターゲットにすることで,T1Dのための新しい治療戦略を提供することができます.
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