コローカライズされたエフェクタおよび調節性T細胞によって強制された免疫ホメオスタシス
Zhiduo Liu1, Michael Y Gerner1, Nicholas Van Panhuys1
1Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA.
Nature
|November 26, 2015
まとめ
調節性T細胞 (Treg細胞) は自己抗原活性化T細胞と集まってフィードバックループを形成する. このTレグ細胞活動は,自己免疫を抑制し,エフェクターT細胞の反応を制限することによって免疫ホメオスタシスを維持する.
科学分野:
- 免疫学
- 細胞生物学
- 自己免疫性
背景:
- FOXP3 ((+)) 調節性T細胞 (Treg細胞) は,自己免疫を予防するために極めて重要です.
- 完全な組織におけるTreg細胞の正確な細胞機構およびin vivoの機能は完全に理解されていません.
- Tレグ細胞が自己特異的なT細胞の活性化を防止するか,すでに活性化した細胞からのダメージを軽減するかは不明である.
研究 の 目的:
- 自己免疫を予防するTreg細胞の細胞内イベントと局所化を調査する.
- 2次リンパ性組織内の自己抗原活性化T細胞への反応におけるTレグ細胞の役割を決定する.
- 免疫ホメオスタシスを維持するためにTreg細胞が利用するフィードバックメカニズムを解明する.
主な方法:
- マウスモデルでの多重量画像
- IL-2への反応としてTreg細胞のクラスタリングとSTAT5のリン酸化の分析.
- トレグ細胞におけるT細胞受容体発現の誘導性アブレーション
主要な成果:
- リン酸化STAT5を発現する高度抑制性Tレグ細胞は,稀なIL-2陽性,自己抗原活性化T細胞と分離したクラスターを形成する.
- Treg細胞におけるSTAT5酸化の局所的なIL-2誘導は,自己免疫反応を制限するフィードバック回路を構成する.
- Tレグ細胞のT細胞受容体発現の障害は,クラスタリングと調節能力を低下させ,制御不能なエフェクターT細胞反応につながります.
結論:
- 自己反応性T細胞は定期的に活性化し サイトカインを産生します
- Treg細胞は物理的にコクラスタリングし,負のフィードバックで初期自己免疫を抑制する.
- トレグ細胞のクラスタリングとT細胞受容体のシグナル伝達は,免疫ホメオスタシスの維持と自己免疫疾患の予防に不可欠です.
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