腸炎を助長する環境要因の特定
Liliana M Sanmarco1, Chun-Cheih Chao1, Yu-Chao Wang2
1Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nature
|October 20, 2022
まとめ
プロピザミドのような環境要因は 炎症性腸疾患 (IBD) を悪化させる可能性があります 新しいシステムアプローチにより,プロピザミドが標的とする免疫細胞の重要なシグナル伝達経路が特定され,IBDの病原性に関する洞察が提供されました.
科学分野:
- 胃腸内科と免疫学
- 環境 健康
- コンピュータ生物学
背景:
- 炎症性腸疾患 (IBD) は慢性的な胃腸疾患で,その罹患率は増加しています.
- 遺伝的要因だけでは IBD を説明することはできません.環境の影響は重要ですが,十分に理解されていません.
- 現存する研究プラットフォームには IBDの環境的なトリガーを特定するための体系的な方法がない.
研究 の 目的:
- IBDの環境要因を特定するための統合システムアプローチを開発し,適用する.
- 環境要因が腸の炎症に影響を与えるメカニズムを解明する.
- IBDおよび関連する炎症性疾患の新たな治療目標を発見する.
主な方法:
- 組み合わせた公共データベース ゼブラフィッシュ化学スクリーン 機械学習 マウスモデル
- システム生物学パイプラインを利用し,環境トリガーの高通量識別を行いました.
- 環境に起因する炎症に関与する分子信号伝達経路を調査した.
主要な成果:
- 腸の炎症を悪化させる要因として 除草剤プロピザミドを特定した
- 免疫細胞におけるアリル炭化水素受容体 (AHR) - 核因子カッパB (NF-κB) - CCAAT増強剤-結合タンパク質β (C/EBPβ) 信号軸を明らかにした.
- プロピザミドは,このAHR-NF-κB-C/EBPβ経路を標的にして炎症を促進することを実証した.
結論:
- IBDの環境要因を発見するための強力なパイプラインを開発しました.
- 腸の炎症に重要な 免疫細胞の信号伝達経路を発見した
- 他の炎症性疾患における環境要因とメカニズムを特定するための枠組みを提供した.
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