拼接异型Foxp3Δ2不同调节tTreg和pTreg恒温
Qianchong Gu1, Xiufeng Zhao1, Jie Guo2
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Science (CAS), Beijing 100101, China; Department of Savaid Medical School, University of Chinese Academy of Sciences (CAS), Beijing 100049, China.
Cell reports
|July 27, 2023
概括
对Foxp3的替代拼接会产生一种活性异型,调节T细胞平衡. 这种被删除的EXON2的Foxp3异型不同地影响来自甲状腺的和外围诱导的调节性T细胞.
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:
- 福克斯p3是调节性T细胞 (Tregs) 主转录因子.
- 人类Foxp3的替代拼接产生了两种异型:全长的和一个被删除的异型.
- 了解Foxp3异型的功能对于Treg生物学至关重要.
研究的目的:
- 调查Foxp3替代拼接对T细胞受体 (TCR) 和互白素-2 (IL-2) 信号传递的功能影响.
- 阐明福克斯p3异型在胸腺衍生Tregs (tTregs) 和外围诱导Tregs (pTregs) 中的差异性作用.
主要方法:
- 使用AlphaFold2进行结构预测.
- 进行了体外实验,以评估蛋白质功能.
- 在pTregs中分析了与RORγt相关的基因表达.
主要成果:
- 福克斯p3的N终端域抑制了DNA结合,这是由外子2介导的过程.
- 福克斯p3Δ2 (被删除的外显子2) 增强了与Batf促进体的结合,导致tTregs中的TCR敏感性降低和IL-2低响应.
- Foxp3Δ2促进了pTregs中的RORγt相关基因表达,从而赋予了竞争优势.
结论:
- 对Foxp3外因子2的替代拼接产生了一个活跃的异型.
- 这种活跃的Foxp3异型在调节tTreg和pTreg平衡中起着不同的作用.
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