パネス細胞は腸の炎症の原点として機能する
Timon E Adolph1, Michal F Tomczak, Lukas Niederreiter
11] Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK [2].
Nature
|October 4, 2013
まとめ
腸内皮質細胞のオートファジーと展開タンパク質応答 (UPR) 経路は,クローン病の予防に不可欠です. 両方の損傷は重度の乳頭炎につながり,病気の発症におけるパネス細胞機能不全を強調する.
科学分野:
- 胃腸内科 胃腸内科
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
背景:
- 自動死性16型1型 (ATG16L1) はクローン病の遺伝的危険因子であり,パネス細胞機能に影響を及ぼします.
- 展開タンパク質応答 (UPR) 転写因子Xボックス結合タンパク質-1 (Xbp1) 変種は,炎症性腸疾患に関連しています.
- 未解決のエンドプラズマ網膜 (ER) ストレスとパネス細胞機能不全は,炎症性腸疾患において一般的です.
研究 の 目的:
- クローン病の文脈で腸内皮質細胞におけるオートファジーとUPRの相互作用を調査する.
- ATG16L1およびXbp1機能障害がイレイトスに寄与するメカニズムを解明する.
- ERのストレス誘発性腸炎におけるパネス細胞の役割を決定する.
主な方法:
- 腸内表 epithelial 細胞におけるオートファジー遺伝子 (Atg16l1,Atg7) またはUPR遺伝子 (Xbp1) の標的切除を施したマウスモデルを使用した.
- パネス細胞機能,ERストレスマーカー,オートファゴソーム形成,炎症信号伝達経路を分析した.
- 病原菌群が病気の発生に与える影響を評価した.
主要な成果:
- 腸内皮質細胞におけるUPRまたはオートファギーのいずれかの障害は,他の経路の補償的関与につながった.
- UPRとオートファギーの組み合わせた欠乏は,クローン病のような重度の自発的なトランスムラル・イレイチスを引き起こした.
- パネス細胞におけるXbp1の欠失により,ERのストレス,オートファギー,および微生物群に依存する自発的なイレイチスが誘発された.
結論:
- オートファジーとUPR経路は,腸内ホメオスタシスを維持し,イレオ炎を予防するために不可欠です.
- ATG16L1は,IRE1αの活性を抑制し,強化されたオートファギーは,ERのストレス誘発性炎症を緩和します.
- イレアル・クローン病は,パネス細胞の特定の疾患であり,不調のUPRとオートファギーを含む可能性があります.
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