Tヘルパー細胞サイトキンは腸幹細胞の再生と分化を調節する
Moshe Biton1, Adam L Haber2, Noga Rogel2
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Cell
|November 6, 2018
まとめ
免疫細胞,特にTヘルパー細胞は,MHCクラスII機構を発現する腸の幹細胞 (ISCs) と相互作用する. これらの相互作用は,ISCの自己再生と分化に影響を与え,感染中に腸内皮質の修復に影響を与えます.
科学分野:
- 胃腸内科
- 免疫学
- 幹細胞生物学
背景:
- 小腸の上皮細胞は,腸の幹細胞 (ISC) から継続的に更新されます.
- 幹細胞の運命を調節するISCニッチ内の免疫細胞の役割はほとんど不明である.
- ニッチ内の付属細胞タイプは,成熟した上皮細胞にISCの分化をサポートします.
研究 の 目的:
- 免疫細胞が腸幹細胞 (ISC) の運命を左右し,上皮の恒常性を研究する.
- ISCの自己再生と分化に関与する特定の免疫細胞サブセットと分子メカニズムを特定する.
- これらの相互作用が,特に感染時に腸内皮質再生にどのように影響するかを理解する.
主な方法:
- 単細胞RNAシーケンシング (scRNA-seq) で,ISCにおける遺伝子発現プロフィールを特定する.
- Tヘルパー細胞とMHCクラスII発現するISCの機能を評価する共培養実験
- ISCの反応を研究するために,Tヘルパー細胞のサイトカインによる腸内器官刺激.
- 感染中にTヘルパー細胞とMHCIIが表皮の分化に与える影響を分析するためのインビオ遺伝的混乱モデル.
主要な成果:
- Lgr5+ ISCの2つのサブセットは,MHCクラスII (MHCII) の機械のための濃縮であることが判明しました.
- MHCII+ Lgr5+ ISCは,CD4+ Tヘルパー (Th) 細胞との共同培養において,非従来の抗原呈現細胞として機能する.
- Th細胞のサイトカインは,Lgr5+ ISCの再生と分化を差異的に調節し,炎症誘発信号は分化を促進し,調節信号はそれを阻害する.
- ISCにおけるTh細胞またはMHCIIの混乱は,感染中に上皮細胞の微分化と腸内上皮細胞の運命に影響する.
結論:
- Tヘルパー細胞とMHCII発現するISCは,腸の幹細胞の行動を調節するクロストークに参加します.
- この免疫-表皮の相互作用は,感染症のような外部刺激に対する組織全体の反応を調整する上で重要な役割を果たします.
- これらのメカニズムの理解は腸疾患と 再生のための治療戦略の開発の鍵です
キーワード:
ISC についてMHCクラスIIMHCIIT ヘルパーT 規制に関するT (レグ)そのエピテリアの分化腸の生物学腸の幹細胞粘膜免疫scRNA-seq について単細胞RNA-seq幹細胞の再生タフット細胞さらに関連する動画
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