生まれながらのリンパ性細胞は,インタールイキン-2 を通して,腸内の調節性T細胞をサポートする
Lei Zhou1,2,3, Coco Chu1,2,3, Fei Teng1,2,3
1Division of Gastroenterology, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Nature
|April 5, 2019
まとめ
インタールイウキン-2 (IL-2) は腸内免疫に不可欠です. グループ3の先天性リンパ球 (ILC3s) はIL-2を生成し,T細胞 (Treg) の調節を維持し,クローン病で障害のある炎症を予防します.
科学分野:
- 免疫学
- 胃腸内科
- 微生物群の研究
背景:
- インタールイキン-2 (IL-2) は,調節性T (Treg) 細胞をサポートすることで,胃腸炎の予防に不可欠です.
- 低用量のIL-2治療は,炎症性腸疾患の潜在的な治療法である.
- 腸内のIL-2の細胞および分子源は不明である.
研究 の 目的:
- 小腸におけるIL-2生成の細胞源と調節経路を解明する.
- 腸内免疫ホメオスタシスとTreg細胞機能の維持におけるIL-2の役割を調査する.
- 人間の炎症性腸疾患における この経路の関連性を調べる
主な方法:
- IL-2の産生を追跡するために,系統特異の遺伝子消去を施したマウスモデルを使用した.
- 小腸のIL-2を生成する細胞を特定するために,偏見のない分析を用いた.
- IL-1β,マクロファージ,MYD88,NOD2がIL-2産生を調節する役割を調査した.
- クローン病患者の小腸組織におけるIL-2およびTreg細胞のレベルを評価した.
主要な成果:
- グループ3の先天性リンパ球 (ILC3s) は小腸におけるIL-2の主な源である.
- ILC3sによるIL-2生成は,MYD88とNOD2経由で微生物群を感知するマクロファージによって生成されるIL-1βによって誘発される.
- ILC3由来のIL-2は,Treg細胞,免疫ホメオスタシス,および経口耐性の維持に不可欠である.
- クローン病の患者では,ILC3sによるIL-2生成の減少とTreg細胞頻度の低下が観察されました.
結論:
- 微生物群,マクロファージ,IL-1β,およびILC3sを含む新しい経路は,小腸におけるIL-2の産生を調節する.
- ILC3由来のIL-2は,腸内免疫調節と経口耐性において重要な役割を果たします.
- ILC3sにおけるこのIL-2経路の調節不良は,クローン病の病原化に寄与する可能性がある.
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