フォリキュラー型デンドリティック細胞は,至る所に存在する周周回性前駆体から生まれます
Nike Julia Krautler1, Veronika Kana, Jan Kranich
1Institute of Neuropathology, University Hospital of Zurich, 8091 Zurich, Switzerland.
Cell
|July 10, 2012
まとめ
フォリキュラー dendritic 細胞 (FDC) は,血小板由来成長因子受容体β (PDGFRβ) を発現する周周先駆体から発生します. これらの前駆体は,リンパ性臓器の外で機能的なFDCに微分化することができ,新しいリンパ性組織の形成を説明します.
科学分野:
- 免疫学 免疫学とは
- 発達生物学 発達生物学について
- 細胞生物学 細胞生物学
背景:
- 葉っぱの樹状細胞 (FDC) は,リンパ性葉っぱの構造と機能に不可欠です.
- FDCの起源と分化経路は,免疫学における長年の疑問である.
- FDCの発達を理解することは,リンパ性組織組織と免疫反応を理解するための鍵です.
研究 の 目的:
- FDCの分化に責任を負う前駆細胞を特定する.
- FDC発現における血小板由来成長因子受容体β (PDGFRβ) の役割を調査する.
- 確立されたリンパ性臓器の外でFDCを形成するための周血管前駆体の可能性を探る.
主な方法:
- PDGFRβを発現する細胞の系統追跡のためにPDGFRβ-Creレポーター遺伝子システムを利用した.
- PDGFRβを発現する細胞の条件式アブレーションを行い,FDC形成の必要性を評価した.
- 脂肪組織に由来する筋血管細胞と腎臓細胞を受容体マウスに移植し,FDCの微分化 in vivo を研究する.
- FDC前駆体膨張におけるリンフォトキシンαとリンパ性組織誘発細胞 (LTi) の役割を調査した.
主要な成果:
- FDCは,PDGFRβ.を発現する至る所に存在する周周血管前駆体 (preFDC) から生じることが実証されました.
- PDGFRβ(+) 細胞がFDCの発達に不可欠であることを,遺伝子アブレーション研究によって確認しました.
- preFDCはリンパ性臓器の外側に存在し,リンパ毒素α過剰発現する腎臓など,適切なシグナリングによって機能的なFDCに微分化することが示されました.
- 脂肪組織から派生したPDGFRβ (((+) ストロマル血管細胞を免疫複合体の罠とB細胞の徴募能力を持つ成熟したFDCに微分化できる細胞として特定した.
- リンパ球欠乏性臓における周周血管FDC前駆体の膨張には,LTi細胞とリンパ毒素が必要であることが明らかになった.
結論:
- フォリキュラーのデンドリティック細胞は,PDGFRβ.を発現する周周先駆体から発生します.
- これらの前駆体は広く分布しており,リンパ性臓器の外で機能的なFDCに微分化し,de novoリンパ性組織形成に貢献します.
- この発見は,FDCの重要な発達経路を明らかにし,免疫系組織と炎症反応を理解するための意味を持つ.
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