HTLV-Iによる自己免疫性慢性関節炎発症機構の解明

• 研究課題/領域番号: 14021022
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 東京大学
• 研究代表者: 岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)
• 研究分担者: 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)
• 研究期間 (年度): 2002
• 研究課題ステータス: 完了 (2002年度)
• 配分額: 6,000千円 (直接経費: 6,000千円); 2002年度: 6,000千円 (直接経費: 6,000千円)
• キーワード: 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

研究概要

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。

研究成果

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