腸内神経系由来IL-18オーケストラ 粘膜障壁免疫
Abigail Jarret1, Ruaidhrí Jackson1, Coco Duizer1
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell
|January 11, 2020
まとめ
腸内神経系 (ENS) は,腸内免疫に不可欠なIL-18を介して抗菌タンパク質 (AMP) を調節する. 神経由来のIL-18は侵入性細菌感染症と粘膜のバリア機能の維持に不可欠です.
科学分野:
- 免疫学
- 神経科学
- 微生物学
背景:
- 粘膜免疫は腸内微生物を維持し,感染症を予防する.
- 免疫細胞と上皮細胞は伝統的に腸内免疫の重要な調節体と見なされています.
- 粘膜免疫における腸神経系 (ENS) の役割はあまり理解されていない.
研究 の 目的:
- ENS が 粘膜 免疫 に 果たす 役割 を 研究 する
- 腸内ニューロンが抗菌タンパク質 (AMP) 反応に寄与するかどうかを判断する.
- ENS が 腸 壁 防御 を 支配 する 仕組み を 解明 する.
主な方法:
- コンフォカル顕微鏡検査と単分子光 in situ mRNAハイブリデーション (smFISH) で,腸内ニューロンにおけるIL-18を検出する.
- 特に腸内ニューロン,免疫細胞,または上皮細胞におけるIL-18の遺伝的消去.
- サルモネラ・タイフィムリウム (S.t.) の感染に関する研究 遺伝子組み換えマウスで
- 偏らないRNA配列と単細胞配列で分子経路を分析する.
主要な成果:
- 腸内ニューロンは,サイトカインIL-18の源として特定されました.
- 腸内ニューロンからIL - 18が削除されたマウスは (他の細胞タイプではなく) S.t. 感染した
- 腸内ニューロンのIL-18は,ゴーグル細胞による恒常的AMP生成に重要であることが判明した.
- 神経由来のIL - 18信号は組織全体の腸内免疫を制御することが示された.
結論:
- ENS は 粘膜 免疫 に 欠かせない 役割 を 果たす.
- 腸内ニューロンのIL-18は,抗菌反応と粘膜壁の整合性の重要な調節剤である.
- 神経由来のIL-18シグナリングをターゲットにすることで,侵入性細菌感染症の管理のための新しい戦略を提供することができます.
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