シュヌリ-2による死亡経路の阻害は,T細胞の発達に不可欠である
Tracy L Staton1, Vanja Lazarevic, Dallas C Jones
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Nature
|April 9, 2011
まとめ
T細胞受容体 (TCR) 誘発死亡経路の抑制は,T細胞発育に極めて重要です. Schnurri-2 (Shn2) は,TCR誘発死亡を抑制し,不適切な陰性選択を防止し,適切なT細胞分化を確保します.
科学分野:
- 免疫学 免疫学とは
- 発達生物学 発達生物学について
- 分子生物学は分子生物学である.
背景:
- T細胞の発達は,T細胞受容体 (TCR) のシグナル解釈に依拠している.
- 信号の強さはチモサイトの運命を決定する:高い信号は負の選択 (死) を引き起こし,中間信号は正の選択 (差別化) を引き起こします.
- TCR信号の強さのレギュレータは知られているが,選択境界を定義する特定のコンポーネントは不明である.
研究 の 目的:
- 陽性と陰性T細胞選択の境界を定義する新しい調節体を特定する.
- T細胞発達中のTCR誘発死亡経路の調節におけるシュヌリ-2 (Shn2) の役割を調査する.
主な方法:
- 遺伝子組み換えマウス (Shn2-/-) を用いたin vivoおよびin vitroの研究.
- タイモサイト細胞運命を分析し,TCR誘発死亡感,信号伝達経路を分析した.
- Shn2欠乏型チモサイトにおけるT細胞の発達と分化に関する評価.
主要な成果:
- Shn2欠乏は,陽性選択信号に対する二重陽性チモサイトの不適切な負の選択につながります.
- Shn2-/-チモサイトは,TCR誘発による死亡に対する感受性が高まっていることを in vitro および in vivo で示しています.
- TCR誘発死亡の遺伝的消去は,Shn2欠乏性チモサイトにおける陽性選択を救済する.
- Shn2はTCRシグナル伝達の下流に作用し,バックス活性化を阻害することによってミトコンドリア死亡経路を抑制します.
結論:
- Schnurri-2 (Shn2) は,TCR誘発死亡経路を阻害する重要な調節体です.
- Shn2は,ポジティブ・セレクション中に不適切なネガティブ・セレクションを防ぐことにより,適切なT細胞発達を保証する.
- Shn2は重要なチェックポイントとして機能し,チモサイトの分化と死亡をバランスとします.
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