ポリシアリレーションは,ケモカインの認識を調節することによって,デンドリット細胞の取引を制御する
Eva Kiermaier1, Christine Moussion1, Christopher T Veldkamp2
1Institute of Science and Technology Austria (IST Austria), Am Campus 1, 3400 Klosterneuburg, Austria.
Science (New York, N.Y.)
|December 15, 2015
まとめ
免疫細胞の密輸には極めて重要です. この研究では,CCR7に対するポリシアル酸が, dendritic 細胞の動きと免疫反応に不可欠なCCL21の認識を可能にします.
科学分野:
- グライコサイエンス
- 免疫学
- 細胞生物学
背景:
- ポリシアリレーションは,神経系の発達と可塑性における役割で主に知られている,グリカンの希少な翻訳後の改変である.
- CCR7のようなケモカイン受容体は,免疫細胞のリンパ性臓器への移行を調節するために重要である.
研究 の 目的:
- 免疫細胞の密輸における ポリシアライゼーションの役割を調査する
- ポリシアリレーションによってケモカイン受容体CCR7の機能と,そのリガンドCCL21との相互作用が変化するかどうかを判断する.
主な方法:
- 野生型およびポリシアリトランスフェラーゼ欠乏症のマウスにおけるCCR7のポリシアリ化分析.
- デンドリット細胞の流通とリンパ節の恒常性の評価
- ケモカイン受容体相互作用の構造機能分析
主要な成果:
- 免疫細胞の密輸のための重要なケモカイン受容体であるCCR7は,ポリシアル酸によって改変されます.
- CCR7のポリシアライゼーションは,そのリガンドであるCCL21の認識に不可欠である.
- ポリシアリルトランスフェラーゼが欠乏したマウスは,デンドリット細胞の輸送が妨げられ,リンパ節の恒常性が妨げられ,炎症的刺激に反応しない.
- 構造分析により,ポリシアル酸は自己抑制型からCCL21を放出する.
結論:
- ポリシアリレーションは,キモカイン受容体の機能を調節することによって,免疫細胞の取引を決定的に調節する.
- この研究は,新種のグリコシレーション媒介免疫細胞取引障害を特定した.
- この発見は,ポリシアル酸がケモカイン受容体相互作用と免疫反応に影響するメカニズムを明らかにしています.
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