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Toll型受容体は,細菌のDNAを認識する.

H Hemmi1, O Takeuchi, T Kawai

  • 1Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Suita.

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|December 29, 2000
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まとめ

CpGモチーフを含む細菌DNAは,免疫細胞を活性化する. 研究者らは,トール型受容体9 (TLR9) がこの反応を媒介することを発見し,自己DNAと外来DNAの区別におけるその役割を強調した.

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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:

  • 非メチル化CpGダイヌクレオチドに富んだ細菌DNAは,哺乳類の免疫細胞を刺激する.
  • 哺乳類のDNAは,CpG周波数とメチル化が低く,免疫刺激活性がない.
  • CpG DNAはT-ヘルパー-1 (Th1) 応答を誘発し,ワクチン補助剤として治療的可能性を示しています.

研究 の 目的:

  • CpG DNA媒介による免疫細胞の活性化に伴う分子メカニズムを解明する.
  • CpG DNAを認識する特定の受容体を特定する.

主な方法:

  • Toll型受容体9欠乏症 (TLR9-/-) のマウスを使用した.
  • スプレノサイト増殖,サイトカイン生成,およびデンドリット細胞の成熟を含む免疫細胞の反応を評価した.
  • CpG DNAチャレンジに対する in vivoの反応を評価した.

主要な成果:

  • TLR9-/-マウスは,胞増殖の欠如,炎症性サイトカイン生成,および dendritic 細胞の成熟を含む,CpG DNAへの反応を示さなかった.
  • TLR9-/-マウスは,致命的なCpGDNA効果に対して抵抗性があり,炎症誘発性サイトカインの上昇を示さなかった.
  • CpG-DNA誘発のTh1応答は,TLR9-/-マウスの体内では廃止された.

結論:

  • CpG DNAに対する細胞の反応は,トール型受容体9 (TLR9) によって決定的に媒介される.
  • TLR9は,脊椎動物の自己DNAとバクテリアDNAを区別するセンサーとして機能します.
  • この発見は,CpG DNAの免疫活性化のメカニズムと,ワクチン開発への影響について明らかにしています.