Mef2dは2型免疫反応とアレルギー性肺炎を強化する
Aydan C H Szeto1, Paula A Clark1, Ana C F Ferreira1
1MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
まとめ
ミオサイト増強因子2d (Mef2d) は,先天性リンパ球 (ILC) とT細胞におけるGATA3発現を調節することによって,タイプ2の免疫を制御する. Mef2dの消去はアレルギー性肺炎から保護する.
科学分野:
- 免疫学
- 分子生物学
- 細胞生物学
背景:
- 生まれながらのリンパ球 (ILC) とTリンパ球は組織ホメオスタシスと免疫反応に不可欠です.
- GATA3転写因子は,ILCとT細胞の発達と2型免疫に不可欠です.
- 2型リンパ球におけるGATA3増調の調節は十分に理解されていません.
研究 の 目的:
- GATA3依存型2型リンパ球の新型調節体を特定する.
- 2型免疫における肌細胞特異増強因子2d (Mef2d) の役割を調査する.
主な方法:
- CRISPRのスクリーンが ILCに搭載されています
- ILC2sとT細胞におけるMef2dの遺伝的削除
- アレルゲン肺の挑戦モデル
- 遺伝子発現とシグナル伝達経路の分析 (例えば,IL-33シグナル伝達,NFAT1転位)
主要な成果:
- CRISPRスクリーンは,ILCにおけるGATA3発現のレギュレータとしてMef2dを特定した.
- ILC2sおよび/またはT細胞におけるMef2dの削除は,アレルゲン誘発肺炎に対する保護を与えました.
- Mef2dはレグナーゼ-1を抑制し,IL-33受容体の増加とIL-33信号伝達の強化につながった.
- Mef2dは,NFAT1核転移と2型サイトカインの生成を促進するために,カルシウムシグナル伝達の後方に作用します.
結論:
- Mef2dは,GATA3依存型2型リンパ球の分化と機能の重要なレギュラーである.
- Mef2dはアレルギー性肺炎において重要な役割を果たします.
- Mef2dを標的とした治療は2型免疫障害の治療策である.
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