源自FOXO的调节天生的免疫恒常性
Thomas Becker1, Gerrit Loch, Marc Beyer
1Development, Genetics & Molecular Physiology Unit, LIMES Institute, University of Bonn, Carl-Troll-Strasse 31, D-53115 Bonn, Germany.
Nature
|January 22, 2010
概括
转录因子FOXO独立于传统免疫路径激活抗菌 (AMP),提供一种新的机制,将新陈代谢和先天免疫联系起来. 这种在人类和虫中保存的过程可能会在能量短缺期间调节宿主防御.
科学领域:
- 这是天生的免疫力.
- 代谢过程中的代谢.
- 细胞应激反应的细胞应激反应
背景情况:
- 抗微生物 (AMP) 对宿主防御病原体至关重要.
- 在Drosophila中,AMP诱导主要由Toll和IMD免疫通路调节.
- 转录因子FOXO调节了抗压力,新陈代谢和衰老.
研究的目的:
- 调查AMP激活是否可以独立于通道和IMD通道发生.
- 探索转录因子FOXO在AMPs调节中的作用.
- 为了确定FOXO介导的AMP调节是否在进化过程中保持.
主要方法:
- 在饥饿,胰岛素信号突变物和小分子抑制剂条件下研究Drosophila的AMP基因激活.
- 在FOXO null突变体和FOXO过度表达模型中分析AMP表达.
- 在drosomycin促进剂上进行分子实验,以评估FOXO结合.
- 在人体细胞 (肺,肠,脏,皮肤) 中进行Drosophila的体内研究和体外研究.
主要成果:
- 福克索直接激活AMP基因,独立于托尔和IMD通路.
- 通过FOXO诱导AMP发生在对诸如饥饿和胰岛素信号等代谢线索的反应中.
- 福克索直接结合于德罗斯辛基的调节区域,诱导转录.
- 这种AMP的FOXO-依赖性调节在包括人类在内的物种中得到保护.
结论:
- 通过FOXO存在一种新的机制来通过代谢和先天免疫之间进行交叉调节.
- 通过FOXO介导的AMP激活在生理压力和能量短缺期间提供了一种防御机制,而不涉及病原体.
- 这一途径提供了一种调节免疫反应的方法,在低能量或压力期间可能最大限度地减少宿主组织损伤.
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