Toll型受容体9のエクトドメインは,機能する受容体を生成するために割れている

Sarah E Ewald¹, Bettina L Lee, Laura Lau

¹Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, 405 Life Sciences Addition, Berkeley, California 94720-3200, USA.

Nature

|September 30, 2008

まとめ

トール型受容体 (TLRs) 7と9は,エンドリゾソームで処理され,エクトドメイン分裂により,その免疫機能が活性化されます. この分裂は自己核酸の認識を妨げ,自己免疫を回避する.

科学分野:

免疫学免疫学とは
細胞生物学細胞生物学
分子生物学は分子生物学である.

背景:

哺乳類のトール型受容体 (TLRs) 3,7,8,9は,微生物の核酸を認識し,免疫反応を誘発する.
TLRsによる自己核酸の制御不良の認識は,自己免疫につながる可能性があります.
TLR7とTLR9の機能を制御する正確な細胞輸送および局所化メカニズムはまだ不明です.

研究の目的:

TLR9とTLR7の細胞内輸送経路を,エンドプラズマ網膜からエンドリゾソームまで解明する.
エンドリゾソーム内のTLR9およびTLR7エクトドメイン分裂の処理と機能的影響を調査する.

主な方法:

マウスマクロファージとデンドリット細胞を活用して,TLR9とTLR7の密輸を追跡した.
分析された受容体エクトドメインの割れ目が,エンドリソソームの区画にある.
完全な長さのTLR9型と割れたTLR9型のリガンド結合とMyD88のリクルート能力を評価した.

主要な成果:

TLR9とTLR7が免疫細胞のエンドリゾソームに輸送される経路を定義した.
TLR9およびTLR7エクトドメインが,エンドリソソーム内でタンパク質分解的に割れていることが示されました.
TLR9の全長ではなく,割れた形をMyD88.8.を勧誘する機能的受容体として特定しました.
断裂を防止したり,表面の局所化を強制したりすると,TLR9が機能しなくなることが示されました.

結論:

TLR9とTLR7のエクトドメイン分裂は,エンドリソソーム内の機能に不可欠である.
この割れメカニズムは,受容体の活性化をエンドリソソムの区間に制限する.
クリーバージは,自己核酸に対するTLR媒介反応を防止し,免疫耐性を維持するための重要な規制戦略として機能します.

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