腸内AHR活動は,ウイルス感染症における肺壁の破壊を防止する

Jack Major^1,2, Stefania Crotta³, Katja Finsterbusch³

¹Immunoregulation Laboratory, Francis Crick Institute, London, UK. jack.major@nyulangone.org.

Nature

|August 16, 2023

まとめ

肺内皮細胞のアリル炭化水素受容体 (AHR) は,インフルエンザによる肺損傷と二次感染から保護します. 食中のAHRリガンドは,この保護機能を維持し,呼吸器疾患における腸肺軸を強調する.

科学分野:

免疫学
細胞生物学
呼吸器医学

背景:

呼吸器ウイルス感染症は肺内皮膜壁を壊し,ガス交換を阻害し,組織損傷を悪化させます.
ウイルス病原体に対する宿主耐性における肺内皮の役割は不明である.

研究の目的:

肺内皮細胞におけるアリル炭化水素受容体 (AHR) が,インフルエンザによる肺血管漏れおよび損傷から保護する役割を調査する.
内皮のAHRシグナル伝達が組織保護と宿主の二次感染に対する感受性に影響を与えるメカニズムを解明する.

主な方法:

内皮特異的なAHRの消去を伴うマウスモデルを使用した.
肺血管の漏れ,免疫細胞の浸透,および上皮細胞の反応を評価した.
アペリン-APJシステムを含むAHR媒介の転写ネットワークを調査した.
食事中のAHRリガンドが肺内皮機能と疾患のアウトカムに与える影響を調査した.

主要な成果:

内皮のAHRの喪失は肺損傷を悪化させ,血管の漏れを増加させ,インフルエンザの感染中に免疫細胞の浸透を促進しました.
内皮のAHR欠乏症は,二次細菌感染症に対する感受性を高めます.
肺内皮質におけるAHRシグナリングは,異常な上皮細胞応答を防止し,バリアの完全性を維持した.
インフルエンザの感染は保護性AHRシグナリングを抑制し,食事によるAHRリガンドはその機能を回復し,疾患耐性を促進した.

結論:

内皮のAHRは肺のバリア免疫とウイルスによる損傷と二次感染に対する保護に不可欠です.
食中のAHRリガンドの影響を受けた腸肺軸は,肺損傷と疾患のアウトカムを調節する上で重要な役割を果たします.
食事を通して内皮のAHR機能を維持することは,重度の呼吸器疾患を予防するために不可欠です.

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