神経ペプチドであるニューロメディンUは,先天性リンパ球と2型炎症を刺激する
Christoph S N Klose1, Tanel Mahlakõiv1, Jesper B Moeller1,2
1Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York 10021, USA.
Nature
|September 5, 2017
まとめ
神経細胞からのニューロメディンU (NMU) は,NMUR1経由で2群の先天性リンパ球 (ILC2) を活性化させる. これは,寄生虫と組織修復に不可欠なタイプ2の免疫反応を促進します.
科学分野:
- 免疫学
- 神経科学
- 胃腸内科
背景:
- 2型サイトカイン (IL-4,IL-5,IL-9,IL-13) はヘルミントに対する免疫,アレルギー性炎症,組織修復に不可欠です.
- グループ2の先天性リンパ球 (ILC2) は,タイプ2のサイトカインの主要な生産者ですが,外部刺激によるILC2応答の調節はよく理解されていません.
研究 の 目的:
- ニューロン信号によるILC2応答の調節を調査する.
- ILC2の活性化と機能におけるニューロメディンU (NMU) とその受容体 (NMUR1) の役割を特定する.
主な方法:
- マウスの腸内におけるILC2sとコリナージックニューロンの同局研究.
- NMUによるILC2sのインビトロ刺激
- ネズミにNMUを vivoで投与する.
- Nmur1欠乏したマウスの分析と養子細胞移植実験.
主要な成果:
- ILC2は選択的にNMU受容体1 (NMUR1) を発現し,NMU発現するニューロンと同局する.
- NMU刺激はILC2sを活性化させ,IL-5,IL-9,およびIL-13の増殖と分泌を誘導する.
- In vivoのNMU投与は,タイプ2のサイトカイン反応,ILC2の活性化,エオシノフィルの募集,寄生虫の排出,および肺炎を促進する.
- Nmur1欠乏はヘルミントの負担を増加させ,NMU-NMUR1軸の役割を確認します.
結論:
- NMU-NMUR1シグナル伝達経路は,腸内神経系と先天的な免疫系との間の新しいリンクを表しています.
- この神経回路は選択的にILC2sを活性化し,粘膜部位で迅速なタイプ2の免疫反応をオーケストラします.
- これらの反応は抗微生物防御,炎症,組織保護に寄与します.
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