異なる線維細胞のサブセットが関節炎の炎症と損傷を誘発する
Adam P Croft1,2, Joana Campos1, Kathrin Jansen3
1Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.
Nature
|May 31, 2019
まとめ
研究者達は関節炎で 炎症や組織損傷を引き起こす 異なる線維芽細胞のサブセットを発見しました これらの特定の線維細胞集団をターゲットにすることで,免疫媒介の炎症性疾患に対する新しい治療法が生まれる可能性があります.
科学分野:
- 免疫学
- 細胞生物学
- リウマトロジ
背景:
- 異なる機能を持つリンパ球のサブセットは,免疫媒介性炎症疾患 (IMID) の標的治療の鍵です.
- IMIDにおける機能的に異なる線維芽細胞サブクラスの存在と役割は,ほとんど不明である.
- 繊維芽細胞は炎症や損傷を含む様々な組織プロセスに関与しているが,その異質性は十分に理解されていない.
研究 の 目的:
- 関節炎で炎症や組織損傷を媒介する 異なる線維芽細胞のサブセットを特定し,特徴づけること.
- 関節炎の臨床前モデルにおけるこれらの線維芽細胞サブセットの機能的役割を調査する.
- IMID の特定のフィブロブラスト集団を標的とした治療の可能性を調査する.
主な方法:
- FAPα+集団内のファイブロブラストサブセットを特定するための単細胞転写分析.
- マウスの関節に特定された線維細胞のサブセットを移植し,その機能を評価する.
- フィブロブラストサブセットの削除の影響を評価するために,解消および持続性のある関節炎のマウスモデルを使用します.
主要な成果:
- 2つの異なる線維細胞群がFAPα+集団内で特定された:FAPα+THY1+免疫エフェクタ線維細胞とFAPα+THY1-破壊性線維細胞.
- FAPα+THY1- 繊維細胞が選択的に骨と軟骨の損傷を介した.
- FAPα+THY1+線維質は,より重症で持続的な炎症性関節炎を誘発し,組織損傷は最小限であった.
- FAPα+ 線維細胞の切除は,関節炎のモデルにおける炎症と骨の侵食の両方を抑制しました.
結論:
- 異なる,解剖学的に局所化された線維細胞のサブセットは,関節炎では重複しない機能を媒介し,炎症または組織損傷を引き起こす.
- これらの発見は,IMIDにおける炎症と組織損傷を調節する標的細胞ベースの治療の可能性を強調しています.
- 免疫媒介の炎症性疾患の効果的な治療法を開発するために,繊維細胞の異質性を理解することは極めて重要です.
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