HTLV-Iによる自己免疫性慢性関節炎発症機構の解明

• Project/Area Number: 14021022
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: 岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)
• Co-Investigator(Kenkyū-buntansha): 須藤 カツ子 東京大学, 医科学研究所, 助手 (50126091) ; 保田 尚孝 東京大学, 医科学研究所, 講師 (90323641)
• Project Period (FY): 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥6,000,000 (Direct Cost: ¥6,000,000); Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
• Keywords: HTLV-I / IL-1Rアンタゴニスト / 関節リウマチ / 自己免疫 / トランスジェニックマウス / ノックアウトマウス / IL-1 / IL-6

Research Abstract

我々はHTLV-I遺伝子を導入したTgマウス(HTLV-I-Tg)を作製し、このウイルスが関節リウマチに良く似た自己免疫性の関節炎を引き起こすことを見いだした。また、この関節炎の発症にはIL-1やIL-6などのサイトカインの過剰発現が重要な役割を果たしていることを示し、さらにIL-1レセプターアンタゴニスト(IL-1Ra)KOマウスも同様の自己免疫性の慢性関節炎になることを示した。IL-1やIL-6を欠損させたHTLV-I-Tgマウスでは自己抗体の産生低下が観察されるとともに、自己抗原に対するT細胞の増殖性の低下が観察された。その原因を明らかにする目的で、T細胞表面上の副シグナル分子の発現を調べたところ、CD40LやOX40の発現が低下していることが明かとなり、HTLV-I-Tgマウスのの関節炎発症にはサイトカインを介したT細胞の活性化が重要な役割を果たしていることが示された。また、マイクロアレイを用いてHTLV-I-TgとIL-1RaKOマウスの関節で発現亢進している遺伝子を検索した結果、両モデルマウスでの遺伝子発現には強い相関が見られた。HTLV-I-Tgで特異的に発現の亢進している遺伝子に注目したところ、機能未知の4遺伝子を含む14遺伝子が同定された。

Research Products

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