TACIとBCMAは,B細胞自己免疫疾患に関与するTNF同類の受容体です
J A Gross1, J Johnston, S Mudri
1Department of Immunology, ZymoGenetics, Seattle, Washington 98102, USA. grossj@zgi.com
Nature
|May 9, 2000
まとめ
B細胞因子zTNF4 (B細胞活性化因子) とその受容体は,狼などの自己免疫疾患と関連しています. zTNF4をTACI-Igでブロックすることは,これらの状態の治療に有望であることが示されています.
科学分野:
- 免疫学 免疫学とは
- 自己免疫疾患 自己免疫疾患
- 分子生物学は分子生物学である.
背景:
- B細胞は,活性化,自己抗体産生,T細胞共刺激を通じて,自己免疫疾患において重要な役割を果たします.
- 腫瘍死滅因子リガンドファミリーのメンバーであるzTNF4 (B細胞活性化因子) は,強力なB細胞共同活性化因子です.
研究 の 目的:
- zTNF4の受容体を特定し,自己免疫疾患におけるその役割を調査する.
- TACI-Igを自己免疫疾患の潜在的な治療薬として評価する.
主な方法:
- トランス遺伝子動物におけるzTNF4の過剰発現.
- 自己免疫性傾向のマウスモデルにおける循環中のzTNF4の定量化.
- zTNF4受容体の識別 (TACIとBCMA).
- 溶性TACI-Ig融合タンパク質でマウスを治療する.
主要な成果:
- zTNF4を過剰に発現したトランス遺伝子動物は,狼のような症状を示し,特定のB細胞集団を拡大しました.
- 循環中のzTNF4濃度の上昇は,マウスモデルでの狼の発症および進行中に観察されました.
- TACIとBCMAはzTNF4受容体として特定されました.
- TACI-Ig治療は,タンパク質尿を減少させ,NZBWF1マウスの生存率を向上させました.
結論:
- zTNF4とその受容体は,システミック・ルプス・エリテマトーサス (SLE) の病原性に関与しています.
- TACI-Igは,ヒトSLEを含む自己免疫疾患の治療に治療的可能性を示しています.
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