树突细胞的L-Myc表达是最佳T细胞原始化所需的
Wumesh KC1, Ansuman T Satpathy1, Aaron S Rapaport1
1Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
Nature
|February 11, 2014
概括
转录因子L-Myc (编码为Mycl1) 对树突细胞的发育和功能至关重要. 在感染期间,L-Myc的损失会损害T细胞的原始化,突出显示其在免疫反应中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- c-Myc和N-Myc是细胞生长和胚胎发育的关键调节剂.
- 相关转录因子L-Myc (编码为Mycl1) 在体内,特别是免疫系统中的作用仍然不清楚.
- 了解Myc家族的对应函数对于破译细胞调节至关重要.
研究的目的:
- 在小鼠中研究L-Myc (Mycl1) 的体内功能.
- 确定免疫细胞中L-Myc的表达模式和调节机制.
- 评估L-Myc缺乏对树突细胞发育和T细胞免疫反应的影响.
主要方法:
- 生成一个Mycl1 ((gfp) 报告者小鼠模型来跟踪L-Myc表达和功能.
- 在发育过程中和响应炎症信号时,分析树突细胞子集中的L-Myc表达.
- 在Mycl1缺陷小鼠中的树突细胞群体的表型特征.
- 在微生物感染期间体内T细胞原始化的评估.
主要成果:
- L-Myc在树突细胞 (DC) 中选择性表达,并由IRF8.8调节.
- 在常见的DC祖先中,L-Myc表达是随着c-Myc表达的减少而启动的.
- 缺少Mycl1的小鼠表现出减少的特定DC子集,包括迁移性CD103 ((+)) 常规DCs.
- 在DC中L-Myc的损失在Listeria monocytogenes和膀性口腔炎病毒感染期间显著损害了体内T细胞原始化.
结论:
- 在特定树突细胞子集的发展和功能中,L-Myc起着关键的,非冗余的作用.
- 在DC中L-Myc的选择性表达和调节表明在免疫反应中具有专门的功能.
- 在炎症期间,L-Myc可能在DC中提供必要的Myc转录活性,促进最佳的T细胞原始化.
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