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決定性NK細胞は,グラヌリシンを伝達し,トロフォブラスト内の細菌を選択的に殺します
Ângela C Crespo1, Sachin Mulik2, Farokh Dotiwala2
1Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; PhD Programme in Experimental Biology and Biomedicine, Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Cell
|August 22, 2020
まとめ
母親の免疫細胞は,抗菌性ペプチドグラヌリシン (GNLY) をナノチューブを通して移し,胎盤を感染から保護する. このメカニズムは 母親と胎児の関わりを傷つけることなく 病原菌を殺し 妊娠を成功させるのです
科学分野:
- 免疫学
- 生殖生物学
- 微生物学
背景:
- 母親の乳首のNK細胞 (dNK) は,胎盤の成功に不可欠です.
- dNK細胞が胎盤を感染から保護し,胎児の耐性を維持する正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- 感染に対する胎盤の防御における dNK 細胞の役割を調査する.
- dNK細胞による抗菌作用のメカニズムを明らかにし,グラヌリシン (GNLY) 転送に焦点を当てた.
主な方法:
- 人間のdNK細胞におけるGNLY発現の分析
- ナノチューブ経由でトロフォブラストにGNLYの転送を調査する.
- ヒトの胎盤培養物,トロフォブラスト細胞系,マウスモデルにおけるListeria monocytogenes (Lm) に対するGNLYの有効性の評価
- Lmに感染したGNLY型と野生型のマウスの妊娠結果の比較
主要な成果:
- 人間のdNK細胞は高レベルのGNLYを発現し,それをナノチューブ経由でエクストラヴィルス型トロフォブラストに転送する.
- 移植されたGNLYは,トロフォブラストの細胞死を引き起こすことなく,細胞内Lmを効果的に殺します.
- GNLY移植は胎盤および胎児組織におけるLm負荷を大幅に減らし,GNLYトランスジェニックのマウスの妊娠の成功を向上させます.
- 周辺のNK細胞 (pNK) も,GNLYの移転を利用して,他の免疫細胞の細菌を除去する.
結論:
- ナノチューブ経由のグラヌリシン伝搬は,母親のdNK細胞が胎盤を細菌感染から守る重要なメカニズムです.
- このGNLYによる防御戦略は 妊婦と胎児の間の壁の整合性を保ち 妊娠を成功させるのです
- この発見は 免疫防御の新たな経路を 母親と胎児のインターフェイスや 他の免疫コンテキストで明らかにしています
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