BATF-JUNは,T細胞におけるIRF4媒介による転写に不可欠である
Peng Li1, Rosanne Spolski, Wei Liao
1Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA. lip3@nhlbi.nih.gov
Nature
|September 21, 2012
まとめ
インターフェロン調節因子4 (IRF4) は,B細胞のPU.1だけでなく,T細胞のAP1複合体と連携しています. このIRF4-AP1の相互作用は,Il10のような遺伝子を調節し,新しい治療標的を提供します.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- トランスクリプション・ファクター規制
背景:
- インターフェロン調節因子4 (IRF4) は,リンパ球の発達と免疫応答に不可欠です.
- IRF4のDNA結合は典型的には弱く,B細胞のPU.1のような因子によって強化され,ETS-IRF複合元素 (EICE) を調節する.
研究 の 目的:
- CD4 ((+)) T細胞におけるIRF4のDNA結合と転写制御の新たなメカニズムを調査する.
- 異なる免疫細胞タイプにおけるPU.1/SPIBを超えたIRF4の協力パートナーを特定する.
主な方法:
- マウスのCD4 ((+)) T細胞とB細胞における複合DNAモチーフへのIRF4結合の分析.
- 活性化タンパク質-1 (AP1) とBATF-JUNファミリータンパク質との協力結合が研究されています.
- 野生型およびノックアウト型T細胞におけるIl10遺伝子を含む遺伝子転写調節の評価.
主要な成果:
- IRF4は意外にもAP1複合体と協力して,AP1-IRF複合元素 (AICE) をCD4のT細胞に結合する.
- BATF-JUNタンパク質は,活性化およびT (H) 17分化CD4 (H) +) T細胞のAICEに対してIRF4と協力する.
- IRF4とAP1/BATFの協同結合は,IL-21調節されたIl10遺伝子の転写を強化する.
結論:
- IRF4は,細胞環境によって異なるDNA結合パートナー (ETSまたはAP1) を利用する.
- これは,T細胞におけるAP1の協力を通じてIRF4媒介の遺伝子調節の新しい方法を明らかにしています.
- この発見は,IRF4に依存する免疫応答を調節するための新しい戦略を示唆しています.
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