ノシセプティブ感受性ニューロンは,インターレウキン23媒介型型皮膚炎を駆動する
Lorena Riol-Blanco1, Jose Ordovas-Montanes1, Mario Perro2
11] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA [2].
Nature
|April 25, 2014
まとめ
感覚神経細胞,特にTRPV1 (((+)) Nav1.8 (((+)) ノシセプターは,皮膚 dendritic 細胞 (DDCs) と相互作用することによって,皮膚の炎症を制御します. この相互作用は,IL-23の産生を調節し,IL-17経路と,牛皮症のような状態における免疫細胞の徴募に影響を与えます.
科学分野:
- 免疫学 免疫学とは
- 神経科学は神経科学である.
- 皮膚科 皮膚科について
背景:
- 皮膚は障壁と感覚器官として機能し,皮膚の樹状細胞 (DDC) や γδT (γδT17) 細胞のような免疫細胞を収容する.
- IL-23によるこれらの細胞の異常な活性化は,牛皮病のような炎症を引き起こす可能性があります.
- 皮の免疫反応を調節する辺縁神経の役割は十分に理解されていません.
研究 の 目的:
- 皮膚の炎症を調節する周辺神経,特に感覚神経の役割を調査する.
- 感覚ニューロンがIL-23の産生と,その後の皮膚の炎症反応に影響を与えるメカニズムを解明する.
主な方法:
- ネズミの皮膚はイミキモドに曝され,IL-23依存型の牛皮症のような炎症を誘発した.
- ノシセプター (TRPV1(+) ナブ1.8(+) 感覚ニューロン) の選択的薬理学的または遺伝的アブレーションが行われました.
- 無傷の皮膚のイメージングは,DDCとノシセプターとの接触を評価するために使用されました.
- IL-23は,ノシセプターから独立してその効果を評価するために,皮質内投与された.
主要な成果:
- TRPV1とNav1.8を発現する感覚ニューロンのサブセットは,イミキモド誘発の皮膚炎を駆動するのに不可欠であることが判明しました.
- 皮膚 dendritic 細胞 (DDC) は,これらの nociceptors と密接な接触で頻繁に観察されました.
- nociceptorsの消去は,DDCsによってIL-23の生成を大幅に減らし,その後のIL-17主導の炎症を減少させた.
- 皮膚内注射のIL-23は炎症を回復し,ノシセプター-DDC通信の必要性を回避しました.
結論:
- TRPV1 ((+) Nav1.8 ((+) ノシセプターは,皮膚の炎症を誘発および調節する上で重要な役割を果たします.
- ノシセプターはDDCと相互作用してIL-23の産生を制御し,それによってIL-23/IL-17経路を調節する.
- これらの発見は,皮膚の免疫反応を調節する皮膚の新たな神経免疫軸を明らかにしています.
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