炎症誘発のIgA+細胞は,肝がんに対する免疫を分解する
Shabnam Shalapour1, Xue-Jia Lin1,2, Ingmar N Bastian1
1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature
|November 17, 2017
まとめ
脂肪肝の慢性炎症は,免疫グロブリンA (IgA+) を生成する細胞を増やすことで癌を促します. これらの細胞は細胞毒性CD8+Tリンパ球を抑制し,早期がん検出を妨げ,腫瘍の成長を促します.
科学分野:
- 免疫学
- ヘパトロジー
- 腫瘍学
背景:
- 早期がんの発症における適応免疫の役割は依然として議論されている.
- 非アルコール性脂肪肝 (NAFLD) は慢性炎症と線維症に関連しています.
- 肝臓に存在する免疫グロブリンA (IgA+) 細胞はNAFLDに蓄積する.
研究 の 目的:
- NAFLDの文脈で肝細胞がん (HCC) の発生におけるIgA+細胞の役割を調査する.
- IgA+細胞が腫瘍の微小環境と免疫監視に影響を与えるメカニズムを解明する.
主な方法:
- NAFLDのヒトとマウスモデルからの肝臓組織の分析.
- プログラム死亡リガンド1 (PD- L1) とインタールイキン-10 (IL-10) の発現を含むIgA+細胞フェノタイプの特徴化.
- 細胞毒性CD8+Tリンパ球機能とHCC発達のIgA+細胞の影響の評価
主要な成果:
- PD- L1 と IL- 10 を発現するIgA+細胞の蓄積がNAFLDで観察された.
- これらのIgA+細胞は肝臓の細胞毒性CD8+Tリンパ球を直接抑制した.
- CD8+ T細胞の枯渇はHCCを加速させ,IgA+細胞の生成を阻害するとともに,肝臓がん発生を弱め,HCCの回帰を促した.
結論:
- IgA+細胞による細胞毒性CD8+Tリンパ球活性化の炎症誘発抑制は,NAFLDに関連したHCCにおける腫瘍促進メカニズムである.
- IgA+細胞の生成をターゲットにすることで,肝臓がんの治療戦略が生まれます.
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