アダプター分子であるTIRAPは,Toll型受容体のシグナル特異性を提供しています
Tiffany Horng1, Gregory M Barton, Richard A Flavell
1Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|November 26, 2002
まとめ
トール型受容体 (TLR) は感染を感知し,免疫反応を活性化します. この研究では,アダプタタンパク質のTIRAPがTLR4のシグナル伝達には重要であるが,TLR5,TLR7,TLR9には重要ではないことが示され,免疫感知における異なる役割を明らかにした.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 哺乳類のトール型受容体 (TLRs) は,感染症の重要なセンサーであり,先天性および適応性免疫反応を開始します.
- TLRは,そのToll/インタールユーキン-1受容体 (Toll/interleukin-1 receptor,TIR) ドメインとアダプタタンパク質MyD88.8を介して信号を発信する.
- TLRsとIL-1受容体がMyD88を通じて信号を送る一方で,個々の受容体の経路は異なります.
研究 の 目的:
- トール型受容体シグナル伝達におけるアダプタータンパク質TIRAPの役割を調査する.
- Tirap遺伝子に欠陥のあるマウスを生成し,特徴づけること.
主な方法:
- ティラップ欠乏マウスの世代.
- 様々なTLRリガンド (TLR4,TLR5,TLR7,TLR9,TLR2,TLR1,TLR6) とIL-1/IL-18.6に対する免疫応答の評価
- サイトカイン生成,NF-kappaB活性化,MAPK活性化の分析.
主要な成果:
- TIRAP欠乏したマウスは,TLR5,TLR7,TLR9リガンド,IL-1/IL-18.に正常な反応を示した.
- LPS (TLR4リガンド) に対する反応として,サイトカイン生成およびNF-kappaB/MAPK活性化における欠陥が観察されました.
- TLR2,TLR1,TLR6リガンドに対する反応の障害は,Tirap欠乏したマウスでも観察された.
結論:
- TIRAPは,トール型受容体シグナル伝達において差異的な役割を果たしています.
- TIRAPはTLR4媒介の免疫反応に不可欠である.
- TIRAPは,個々のTLRのダウンストリームシグナリングの特異性に寄与する可能性があります.
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