PIRは先天的な骨髄細胞の記憶を非自己MHC分子に媒介する
Hehua Dai1, Peixiang Lan2,3, Daqiang Zhao1
1Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
まとめ
モノサイトやマクロファージのような先天性骨髄細胞は,特定の抗原に対する免疫的記憶を発達させることができます. ペアリングされた免疫グロブリン型受容体 (PIR-As) を含むこの発見は,移植結果を改善する可能性があります.
科学分野:
- 免疫学
- 移植生物学
- 生まれつきの免疫
背景:
- 適応性リンパ球細胞は抗原に対する免疫的記憶を示します.
- 生まれながらの骨髄細胞の記憶の存在は ほとんど未調査のままです
- 骨髄細胞の記憶を理解することは 移植を進めるために不可欠です
研究 の 目的:
- 先天的な骨髄細胞が抗原特異記憶を持つかどうかを調査する.
- 骨髄細胞の記憶の基礎にある 分子機構を特定する
- 骨髄細胞の記憶を 移植する治療の可能性を探るため
主な方法:
- モノサイトとマクロファージのマウスモデル
- 抗原刺激と再挑戦
- ペアリングされた免疫グロブリン型受容体 (PIR-As) の遺伝的消去と阻害
- 腎臓と心臓移植におけるアロ移植拒絶の評価
主要な成果:
- ネズミの単細胞とマクロファージは,メジャー・ヒストコンパティビリティ・コンプレックスI (MHC- I) 抗原に特異的な記憶を示した.
- このMHC- I特異的な記憶応答には,ペアリングされた免疫グロブリン型受容体 (PIR- As) が不可欠であることが確認された.
- PIR- Aの削除またはPIR- A/ MHC- Iの相互作用の遮断は,アロ移植の拒絶を著しく減少させた.
結論:
- 生まれながらの骨髄細胞はアロアンチゲン特異の免疫記憶を持っている.
- PIR-Aは,骨髄細胞におけるこの記憶応答を媒介する重要な受容体である.
- PIR-Aをターゲットにすることで 生まれつきの免疫記憶を調節することで 移植結果を向上させる新しい戦略が提供されます
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