支氣管上皮細胞によるアポプトシス細胞クリアランスは,呼吸道炎症に重大な影響を及ぼします

Ignacio J Juncadella¹, Alexandra Kadl, Ashish K Sharma

¹Carter Immunology Center, University of Virginia, Charlottesville, Virginia 22908, USA.

Nature

|December 14, 2012

まとめ

呼吸道上皮細胞は,Rac1信号伝達を通じてアポプトティック細胞をクリアし,炎症を軽減します. このプロセスの欠陥は,アレルギー性呼吸道反応を悪化させ,Rac1を強調する.

科学分野:

免疫学免疫学とは
細胞生物学細胞生物学
呼吸器医学とは

背景:

肺上皮細胞は,呼吸道アレルゲンに対する免疫反応を調節する.
呼吸道上皮細胞のアポトーシスは,アレルゲン被曝時に起こりますが,クリアランスメカニズムとその炎症効果は十分に理解されていません.

研究の目的:

呼吸道上皮細胞がアポプトシス細胞をクリアする役割を調査する.
このプロセスにおける小さなGTPase Rac1の関与と,呼吸道炎症とアレルゲンに対する免疫反応への影響を決定する.

主な方法:

特定の呼吸道上皮細胞におけるRac1の誘導式消去を伴うマウスモデルを使用した.
アポプトシス細胞の吸収,サイトカインの産生,および鼻内アレルゲン誘発後の炎症反応の評価 (家粉のエキス,オバルブミン).
測定されたTh2サイトカイン,インタールイキン-10 (IL-10),IL-33およびヌオサイト型細胞集団.

主要な成果:

Rac1欠乏の呼吸道上皮細胞は,アポプトシス細胞の吸収が損なわれ,抗炎症性サイトカインの分泌が変化していた.
Rac1欠乏症は,呼吸道炎症を悪化させ,Th2とIL-33のレベルを上昇させ,呼吸道過剰反応を引き起こした.
IL-10の投与は,Rac1欠乏したマウスの炎症性フェノタイプを改善した.

結論:

呼吸道上皮細胞によるRac1依存の包み込みは,抗炎症環境の確立に不可欠です.
呼吸道上皮細胞クリアランスの欠陥は,一般的なアレルゲンに対する炎症反応に寄与する.
この研究は,Rac1が呼吸道炎症と免疫ホメオスタシスを調節する新たな役割を明らかにしています.

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