在T细胞中,BATF-JUN对于IRF4介导的转录至关重要
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
概括
干扰素调节因子4 (IRF4) 与T细胞中的AP1复合体合作,而不仅仅是B细胞中的PU1. 这种IRF4-AP1相互作用调节像Il10这样的基因,提供新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 转录因子法规转录因子法规
背景情况:
- 干扰素调节因子4 (IRF4) 对淋巴细胞发育和免疫反应至关重要.
- IRF4的DNA结合通常很弱,由B细胞中的PU.1等因素增强,以调节ETS-IRF复合元件 (EICE).
研究的目的:
- 研究IRF4DNA结合和转录调节在CD4 ((+) T细胞中的新机制.
- 在不同类型的免疫细胞中识别PU.1/SPIB以外的IRF4的合作伙伴.
主要方法:
- 分析IRF4与小鼠CD4 ((+) T细胞和B细胞中的复合DNA基因的结合.
- 研究了与激活蛋白-1 (AP1) 和BATF-JUN家族蛋白质的合作结合.
- 在野生类型和淘汰赛T细胞中评估了基因转录调节,包括Il10基因.
主要成果:
- 意想不到,IRF4与AP1复合体合作,在CD4 T细胞中结合AP1-IRF复合元件 (AICE).
- BATF-JUN蛋白与IRF4合作,在激活的AICE和T(H) 17分化的CD4(+) T细胞中进行AICE.
- 合作结合IRF4和AP1/BATF增强了IL-21调节的Il10基因的转录.
结论:
- 根据细胞环境,IRF4使用不同的DNA结合伙伴 (ETS或AP1).
- 这揭示了通过T细胞中的AP1合作来调节IRF4介导的基因的新模式.
- 研究结果表明,有新的策略可以调节依赖IRF4的免疫反应.
相关概念视频
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