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: 13226021
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas (C)
• 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): 宝来 玲子 東京大学, 医科学研究所, 助手 (20313091) ; 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): 2001
• Project Status: Completed (Fiscal Year 2001)
• Keywords: HTLV-I / トランジェニックマウス / IL-1 / IL-6 / 自己免疫疾患 / 関節リウマチ / CD40L / OX40

Research Abstract

HTLV-IはATLの原因ウイルスとして発見されたが、HAM/TSPやシェグレン症候群など免疫系の関与が考えられる他の疾患への関与も示唆されている。我々はHTLV-Iのtax遺伝子を導入したトランスジェニクマウス(HTLV-I-Tg)を作製し、このウイルスが関節リウマチによく似た慢性関節炎を引き起こすことを初めて示した。さらに、関節炎発症に自己免疫が関与していることを見いだし、HTLV-Iが自己免疫を引き起こすことを明らかにした。本研究ではHTLV-I-Tgマウスモデルを用い、免疫異常の発症機構を解明することを目的とした。HTLV-I-Tgの炎症局所でIL-1やIL-6、TNF-αといった炎症性サイトカインが亢進していることを以前に報告したが、そのサイトカインの役割を明らかにする目的で、このHTLV-I-Tgのサイトカイン遺伝子を欠損させたところ、IL-1とIL-6が発症に重要であることが明らかとなった。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共に、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らかとなった。これらの結果から、HTLV-I-Tgマウス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。

Research Products

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