T細胞は肺で認可され,中枢神経系に入る
Francesca Odoardi1, Christopher Sie, Kristina Streyl
1Institute for Multiple Sclerosis Research, Department of Neuroimmunology, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, 37073 Göttingen, Germany.
Nature
|August 24, 2012
まとめ
以前から考えられていたこととは違って,T細胞の爆発は中枢神経系 (CNS) に容易に入らない. 代わりに,肺組織のレジデンスがT細胞を再プログラムし,中枢神経への移住を可能にし,多発性硬化症のような自己免疫疾患に貢献します.
科学分野:
- 神経免疫学 神経免疫学とは
- 自己免疫疾患 自己免疫疾患
- 携帯電話の密輸について
背景:
- 血脳障壁 (BBB) は通常,中枢神経系 (CNS) を外周免疫細胞から保護する.
- 多発性硬化症では,T細胞がBBBを破って,中枢神経系の自己免疫を誘発すると考えられている.
- このモデルは,T細胞がBBBを準備して,その後の免疫細胞の侵入を想定しています.
研究 の 目的:
- 実験的な自己免疫性脳内炎において,T細胞がCNSに最初に侵入するメカニズムを調査する.
- T細胞爆発がCNSへの侵入のためにBBBの事前活性化を必要とするかどうかを判断する.
- 周辺臓器,特に肺のT細胞活性化と中枢神経系の移動における役割を調査する.
主な方法:
- 実験的自己免疫性脳髄炎のルイスのラットモデルを使用した.
- 移転されたT細胞ブラストを静脈内および内.
- 遺伝子発現プロファイルとT細胞の移動パターンを分析した.
- T細胞の再プログラムにおける肺組織と関連するリンパ性構造の役割を調査した.
主要な成果:
- 静脈経由で伝達されたT細胞ブラストは,効率的に中枢神経系に入ったり,BBBを準備したりしませんでした.
- T細胞ブラストは,肺組織に一時滞在した後,中枢神経系への侵入能力を獲得した.
- 肺在留は,ニンジュリン1のような細胞移動と粘着分子のアップレギュレーションを含む,重要な遺伝子発現変化を誘導した.
- 活性化および静止状態のミエリン反応性T細胞は,肺で発見され,局所刺激により,増殖および中枢神経系への移住が起こりました.
- 直接呼吸道に移植されたT細胞は,同様の移動パターンを示し,病原性を保持しました.
結論:
- 肺は,T細胞の活性化と再プログラムのための重要な場所として機能し,中枢神経系への移動を促進します.
- 中枢神経系へのT細胞の侵入は,最初のBBB製剤に依存するのではなく,肺に誘発された移住特性に依存する.
- この発見は,中枢神経系の自己免疫の発症の伝統的なモデルに異議を唱え,T細胞媒介による自己免疫反応のオーケストラ化における肺の役割を強調しています.
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