B細胞活性化因子の中和 動脈硬化症を悪化させる
Dimitrios Tsiantoulas1,2, Andrew P Sage3, Laura Göderle1,2
1Department of Laboratory Medicine, Medical University of Vienna (D.T., L.G., M.O.-K., F.P., C.J.B.).
Circulation
|June 3, 2018
まとめ
B細胞活性化因子 (BAFF) による治療は,B細胞ではなく,骨髄細胞に影響を与えることで,ネズミの動脈硬化症を予期せぬほど悪化させた. これは,心臓血管疾患に対する潜在的な臨床的影響を持つ,B細胞とは独立したBAFFの新たな抗炎症作用を明らかにしている.
科学分野:
- 免疫学
- 心血管科学
- ゲノミクス
背景:
- 動脈硬化性心血管疾患は 動脈のプラークの蓄積によって引き起こされる 世界の主要な死因です
- ゲノム研究では,冠動脈疾患におけるB細胞活性化因子 (BAFF) 経路が関与している.
- 自己免疫疾患に対する既存の抗BAFF治療は,潜在的に心血管上の利点を示唆しますが,動脈硬化に対する直接的な効果は不明です.
研究 の 目的:
- 動脈硬化に対する BAFF 中和の影響を調査する.
- BAFFが動脈硬化症の進行に影響を与えるメカニズムを解明する.
主な方法:
- アポエ/ Ldlr/ マウスの抗BAFF抗体による治療
- BAFF受容体,トランスメブラン活性化器,カルシウム調節器およびサイクロフィリンリガンドインタラクター (TACI) が欠けている動脈硬化症に罹患するマウスの分析.
- 骨髄細胞特異性およびB細胞特異性 TACI 削除の調査
主要な成果:
- B細胞の枯渇にもかかわらず,抗BAFF抗体の治療は逆説的に動脈硬化症を増加させた.
- 骨髄細胞特異的なTACI消去は,B細胞特異的な消去ではないが,動脈硬化も増加した.
- BAFF- TACIシグナリングは,マクロファージ IRF7依存型トール型受容体9の反応とプロアテロゲン性CXCL10の産生を抑制することが判明した.
結論:
- BAFFは動脈硬化症において,B細胞独立の抗炎症的役割を果たします.
- これらの発見は,心血管リスクの管理に重大な臨床的影響を及ぼす可能性があります.
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