酸化された低密度リポプロテインに対する経口耐性の誘導は,動脈硬化症を緩和します
G H M van Puijvelde1, A D Hauer, P de Vos
1Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands. puijvelde@lacdr.leidenuniv.nl
Circulation
|October 25, 2006
まとめ
酸化低密度リポプロテイン (oxLDL) の経口投与は,耐性を誘発し,マウスの動脈硬化症の発症を減少させた. これには,調節性T細胞の活性化が含まれ,動脈硬化症の新たな治療の可能性を示唆しました.
科学分野:
- 免疫学 免疫学とは
- 心血管研究 循環器科の研究
- 動脈硬化症の研究研究
背景:
- マクロファージによる酸化低密度リポプロテイン (oxLDL) 処理はT細胞を活性化し,動脈硬化に寄与します.
- 経口による耐性誘導と調節性T細胞活性化は,動脈硬化症の潜在的な治療戦略を提供します.
研究 の 目的:
- 動脈硬化症の予防と治療におけるoxLDLを用いた経口耐性誘導の有効性を調査する.
- オックスLDL誘発の経口耐性における規制性T細胞の役割とそのアテロゲネシスへの影響について調べる.
主な方法:
- アテロゲネシス前にoxLDLまたはMDA-LDLを使用したLDL受容体/-マウスの経口耐性誘発.
- 動脈硬化症の発症および進行に対する経口耐性の影響を評価した.
- 調節性T細胞集団 (CD4+CD25+Foxp3+) とそのサイトカイン生成 (TGF-β) の定量化された変化.
- 動脈硬化性プラークにおける重要な調節性T細胞マーカー (Foxp3,CTLA-4,CD25) のmRNA発現を分析した.
主要な成果:
- オックスLDLへの経口耐性は,マウスの動脈硬化の発症 (30-71%) と進行 (45%) を著しく弱めた.
- 誘発された耐性により,とリンパ節のCD4+ CD25+ Foxp3+細胞が増加し,oxLDL特異のTGF-β生成が強化されました.
- オックスLDLの経口投与後のプラークでは,Foxp3,CTLA-4,CD25のmRNA発現の増加が観察されました.
- MDA-LDLに対する耐性は,アテロゲネシスに影響しませんでした.
結論:
- 経口投与によって活性化されるoxLDL特異の調節性T細胞は,動脈硬化に関与するoxLDL特異のT細胞に対抗することができます.
- オックスLDLへの経口耐性誘導は,アテロゲネシスの免疫応答を調節するための有望な戦略です.
- このアプローチは,動脈硬化症の治療のための新しい治療法を提供します.
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