慢性リンパ球炎症は,プライオンの臓器トロピズムを特定する
Mathias Heikenwalder1, Nicolas Zeller, Harald Seeger
1Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland.
Science (New York, N.Y.)
|January 22, 2005
まとめ
慢性的な炎症は,プリオンが新しい臓器に蓄積する原因となります. これはリンパ毒素に依存する経路を経由して発生し,プリオン病の伝染リスクを潜在的に高めます.
科学分野:
- 神経免疫学 神経免疫学とは
- プリオン生物学の学科
- 病原発生研究 病原発生研究
背景:
- プリオン (誤った折りたたまれたタンパク質) は通常,神経組織とリンパ球組織を標的にします.
- 炎症誘発性サイトカインと免疫細胞は,リンパ性組織におけるプリオン複製に不可欠です.
研究 の 目的:
- 炎症状態が非リンパ性臓器におけるプリオン病原性に影響するかどうかを調査する.
- プリオン組織分布の拡大における炎症の役割を決定する.
主な方法:
- 誘発性炎症性腎臓,臓,または肝臓疾患を有するマウスにプリオンを投与した.
- プリオン蓄積,リンフォトキシン発現,炎症組織におけるFDC-M1+細胞の存在を分析した.
- リンフォトキシンアルファまたはその受容体が欠乏したマウスのプリオン病原性を調べた.
主要な成果:
- 慢性リンパ球性炎症は,以前にプリオンフリーであった臓器にプリオン蓄積を可能にしました.
- 炎症的焦点には,リンパトキシンの上昇調節と子宮外FDC-M1+細胞誘導が関連していることが示された.
- リンフォトキシンアルファまたはその受容体が欠けているマウスは,PrPScを蓄積したり,感染性を示したりしませんでした.
結論:
- 慢性炎症状態は,プリオンの組織分布を拡大する可能性があります.
- リンパ毒素のシグナル伝達は,炎症した非リンパ性臓器におけるプリオン蓄積に極めて重要です.
- 炎症はプリオン病の伝播を変化させる可能性があります.
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