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超强增强剂在T细胞中划分与疾病相关的调节节点
Golnaz Vahedi1, Yuka Kanno1, Yasuko Furumoto2
1Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Nature
|February 18, 2015
概括
在T细胞中的超级增强剂 (SE) 识别了关键的免疫调节剂和疾病基因. 关键抑制剂BACH2控制这些SE,为诸如类风湿性关节炎之类的免疫疾病提供新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 增强剂控制基因表达和细胞身份.
- 超级增强剂 (SE) 对细胞身份基因和疾病风险至关重要.
- CD4 ((+) T细胞对于免疫和自身免疫是至关重要的.
研究的目的:
- 使用SE映射识别T细胞中的关键监管节点.
- 了解SEs在T细胞特异性和功能中的作用.
- 调查T细胞SE和免疫媒介疾病之间的联系.
主要方法:
- 分析小鼠T细胞超强增强剂 (SE) 地图.
- 在T细胞中识别SE结构的基因.
- 与疾病相关的单核酸多形态 (SNP) 的丰富分析.
- 对JAK抑制剂tofacitinib的T细胞反应的评估.
主要成果:
- 细胞因子和细胞因子受体是主要的SE相关基因.
- 巴赫2位点被确定为最突出的T细胞SE.
- BACH2抑制了SE架构对T细胞生物学至关重要的基因.
- T细胞SEs被丰富为类风湿性关节炎风险SNP.
- 托法西替尼治疗不成比例地影响了SE相关的类风湿关节炎风险基因.
结论:
- 在T细胞中的SE突出显示关键的调节节点,包括细胞因子和BACH2.
- BACH2作为一个"守护者"转录因子,控制SE相关基因.
- 对于免疫疾病风险变体,T细胞SE被丰富.
- 针对SE的药理干预可以为免疫障碍提供治疗策略.
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