IRF-7は,タイプIインターフェロン依存性免疫応答の主調節体です
Kenya Honda1, Hideyuki Yanai, Hideo Negishi
1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|April 1, 2005
まとめ
転写因子IRF-7は,ウイルス感染症に対するタイプIインターフェロン (IFN-alpha/beta) 反応に不可欠です. IRF-7は,IFN誘導経路を調節することにより,先天性および適応性免疫の両方を制御します.
科学分野:
- 免疫学 免疫学とは
- ウイルス学 ウイルス学 ウイルス学
- 分子生物学は分子生物学である.
背景:
- I型インターフェロン (IFN-alpha/beta) は,抗ウイルス免疫に不可欠です.
- IFN応答は,細胞性ウイルス検出またはトール型受容体9 (TLR9) 信号によって誘発される可能性があります.
- MyD88アダプタータンパク質は,TLR媒介のIFN誘導に関与しています.
研究 の 目的:
- IFN-α/β遺伝子誘導における転写因子IRF-7の役割を調査する.
- MyD88独立系とMyD88依存系の両方のIFN経路におけるIRF-7の必要性を決定する.
- プラズマチトイド dendritic 細胞の反応と適応免疫における IRF-7 の機能を明らかにする.
主な方法:
- 遺伝子欠乏マウス (Irf7-/- と Myd88-/-) を利用した.
- フィブロブラストにおけるIFN-α/β遺伝子誘導とマウスにおける血清IFNレベルを評価した.
- プラズマシトイド dendritic 細胞と CD8+ T 細胞の応答で IFN の生産を評価した.
主要な成果:
- IRF-7は,IFN-alpha/beta遺伝子の誘導には,ウイルス活性化経路 (MyD88独立) とTLR活性化経路 (MyD88依存) の両方で不可欠である.
- Irf7-/-マウスはMyd88-/-マウスと比較してウイルス感染症に対する脆弱性が高く,血清のIFN濃度が低下しています.
- プラズマシトイド dendritic 細胞における TLR9 活性化による堅固な IFN 生成は,完全に IRF-7 に依存し,CD8+ T 細胞の反応を制御します.
結論:
- IRF-7は,タイプIインターフェロン反応のすべての側面を制御するマスターレギュレータです.
- IRF-7は,全身の先天性抗ウイルス免疫と,プラズマサイトイド dendritic 細胞によって媒介される適応免疫反応の両方にとって重要です.
- MyD88-IRF-7経路は,TLR9誘発のIFN生成と,その後のT細胞免疫にとって不可欠である.
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