メタボライトが誘発するタフ細胞-ILC2回路が小腸の改造を促す

Christoph Schneider¹, Claire E O'Leary¹, Jakob von Moltke¹

¹Department of Medicine, University of California San Francisco (UCSF), San Francisco, CA 94143, USA.

Cell

|June 12, 2018

まとめ

小腸のタフト細胞-ILC2回路は寄生虫に反応して腸を改造します A20によって制御されるこの回路は,新しいヘルミントの感染を防ぐためにサクシネートセンシングを使用します.

科学分野:

免疫学
胃腸内科
微生物学

背景:

腸内寄生虫に対する上皮の反応には,小腸のタフ細胞-ILC2回路が不可欠です.
タフト細胞は病原体を感知し,IL-25経由で先天性リンパ性細胞タイプ2 (ILC2) を活性化します.
ILC2は,A20 (Tnfaip3) によって陰性調節されるIL-25受容体を発現する.

研究の目的:

タフット細胞-ILC2回路の調節におけるA20の役割を調査する.
この回路が腸の改造と免疫を媒介するメカニズムを解明する.
回路の活性化に関与する代謝信号を特定する

主な方法:

ILC2のA20の遺伝子操作
小腸の形状と免疫細胞の分析
腸のメタボロミック分析
特定の代謝産物と受容体対抗剤を用いた機能分析

主要な成果:

ILC2sのA20欠乏は,タフト細胞-ILC2回路を自発的に活性化し,小腸の延長と再構成につながります.
サーキットの活性化は,乳児の離乳とプロチコモナスのコロニー化に関連しており,これはルミナルサクシネートを増加させる.
サクシネートは,タフト細胞GPR91によって感知され,TRPM5とIL-25に依存する経路を通じてILC2sを活性化します.
この再構成は,同時に発生する免疫を模倣して,二次ヘルミントの感染に対する耐性をもたらします.

結論:

タフト細胞とILC2sを含む代謝センサー回路が腸の適応と免疫を調節する.
サクシナートは,この回路の活性化に重要な代謝物質として作用する.
タフット細胞-ILC2-スッキナート軸は,新しいヘルミンスの感染に対する耐性を提供し,光病共生体の管理のための進化したメカニズムを示唆する.

キーワード:

A20 について IL-25 について ILC2s について TRPM5 についてトリチコモナス併発性免疫ヘルミンツサクシネートサクシネート受容体タフット細胞

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