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皮膚に宿る先天性リンパ細胞は,病原性エフェクタ状態に収束する
Piotr Bielecki1,2, Samantha J Riesenfeld3,4,5, Jan-Christian Hütter6
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. piotr.stanislaw.bielecki@gmail.com.
Nature
|February 4, 2021
まとめ
皮の先天性リンパ球 (ILCs) は,イール23シグナル伝達によって psoriasis の間に病原性ILC3のような状態に移行することができます. 組織に存在するILCは,この炎症に不可欠であり,動的免疫細胞の可塑性を強調する.
科学分野:
- 免疫学
- 細胞生物学
- 皮膚科
背景:
- 組織に宿る先天性リンパ球 (ILC) は,バリア免疫と局所反応において重要な役割を果たします.
- ILCは,転写因子とサイトカインプロファイルに基づいてサブタイプ (ILC1,ILC2,ILC3) に分類されます.
- 牛皮病では,ILC3に関連したサイトカインIL-17とIL-22が,IL-23によって誘発され,皮膚の炎症に寄与する.
研究 の 目的:
- 牛皮質炎症は,既発症したILCによって,または細胞状態の移行によって引き起こされるかどうかを調査する.
- 牛皮病の誘導中の皮膚のILCのダイナミックな転写風景を特徴づける.
主な方法:
- IL-23またはイミキモドを使用したマウスにおける牛皮病の誘発.
- 皮膚のILCの単細胞RNA配列化 (scRNA-seq) が時間的に行われている.
- In vitro実験,単細胞ATACシーケンシング (scATAC-seq),およびin vivo運命マッピング
主要な成果:
- 牛皮の炎症は皮膚のILCのスペクトルを再構成し,病原性ILC3のような状態に収束します.
- 組織に定着したILCは,循環中のILCではなく,病理を誘導するのに十分でした.
- scRNA-seqは,疾患誘導時にILC3のようなフェノタイプにシフトする,流動的なILC状態の転写連続性を明らかにした.
- 静止型およびILC2のILC状態は,移行の可能性があることが確認されました.
結論:
- 皮膚のILCは,炎症誘発に反応して,驚くべき可塑性を発揮します.
- 免疫細胞のダイナミックな適応は 健康な組織に 制御されない場合 病理的な改造につながります
- 炎症性皮膚疾患の 標的型治療法の開発には 細胞状態の変化を理解することが 極めて重要です
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