膠質細胞由来ニューロレギュレータは3型先天性リンパ球と腸内防御を制御する
Sales Ibiza1, Bethania García-Cassani1, Hélder Ribeiro1
1Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
Nature
|July 14, 2016
まとめ
グリア細胞とグループ3の先天性リンパ球細胞 (ILC3) は,腸の防御を調節するユニットを形成する. ニューロトロフィック要因は先天的なインタールイキン22 (IL-22) 産生を制御し,炎症と感染感受性に影響を与えます.
科学分野:
- 免疫学
- 神経科学
- 胃腸内科
背景:
- 3群の先天性リンパ球 (ILC3) は,粘膜免疫の重要な調節体である.
- ILC3が微小環境を感知し反応するメカニズムは完全に理解されていません.
研究 の 目的:
- ILC3媒介の腸内防御における 膠質細胞と神経栄養因子の役割を調査する.
- ILC3 膠質細胞の伝達経路を解明する.
主な方法:
- ILC3とグリアル細胞の標的遺伝子の欠損を有するマウスモデル (Ret,Myd88).
- 免疫細胞集団,サイトカイン産生 (IL-22),上皮の反応性,腸内微生物群の分析.
- p38 MAPK/ERK-AKTとSTAT3を含むシグナリングカスケードの調査
主要な成果:
- 腸内 ILC3 は神経縮受容体 RET を発現し,ILC3 のRet 剥離はIL-22の産生,上皮の防御を阻害し,炎症や感染症に対する感受性を高めます.
- ILC3に隣接する膠質細胞は,p38 MAPK/ERK-AKTとSTAT3経由でIL-22の産生を調節する神経栄養因子を産生する.
- グリアル特異的なMyd88の消去はIL-22の産生を阻害し,腸内炎症と感染症を悪化させる.
結論:
- ニューロトロフィック因子によって制御される 新しい膠質-ILC3-上皮細胞単位が 腸の防御を制御します
- 膠質細胞は神経栄養因子を通して神経細胞と免疫信号を統合する中央調節体として機能する.
- この発見は 粘膜の障壁で生まれつきの免疫を 調節するための新しい経路を 強調しています
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