AP-1转录因子 Batf 控制了 T(H) 17 的分化
Barbara U Schraml1, Kai Hildner, Wataru Ise
1Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.
Nature
|July 7, 2009
概括
转录因子BATF对于T辅助细胞17 (T(H) 17的发展至关重要,这些细胞对宿主防御至关重要,并与自身免疫性疾病有关. 失去BATF会影响T(H) 17的分化,并防止实验性自身免疫脑膜炎.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 激活蛋白1 (AP-1) 转录因子通过二分化调节基因表达.
- 作为AP-1家族的成员,BATF缺乏正规激活域,此前被认为可以抑制AP-1活动.
- 辅助T细胞17 (T(H) 17对于免疫力至关重要,但也参与自身免疫病原发生.
研究的目的:
- 研究AP-1转录因子BATF在T(H) 17细胞分化中的作用.
- 阐明BATF影响T(H) 17细胞发育和功能的分子机制.
主要方法:
- 在Batf缺乏的小鼠中分析T(H) 17细胞分化.
- 评估T(H) 1和T(H) 2细胞的分化.
- 研究与T(H) 17分化相关的基因表达 (例如,RORgamma t,IL21).
- 染色体免疫沉 (ChIP) 用于确定在基因促进体和基因间元素上的BATF结合位.
主要成果:
- 蝙蝠-/-) 小鼠表现出正常的TH1和TH2分化,但TH17细胞分化的显著缺陷.
- Batf(-/-) T细胞未能诱导T(H) 17发育所需的RORgamma t和IL21等关键因素.
- 过度表达IL21或RORgamma t并没有完全挽救Batf(-/-) T细胞中IL17的产生.
- BATF直接与Il17,Il21和Il22的促进体结合,以及在Il17a-Il17f位点内的保存的跨基因元素.
结论:
- 最佳可利用技术 (BATF) 是T(H) 17细胞分化不可或缺的.
- BATF作为T(H) 17细胞身份和功能的关键调节者.
- 这些发现揭示了BATF在调节由T(H) 17细胞介导的炎症反应方面具有新的,至关重要的作用.
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