在Foxp3基因中保存的非编码DNA元素在调节性T细胞命运中的作用
Ye Zheng1, Steven Josefowicz, Ashutosh Chaudhry
1Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington 98195, USA.
Nature
|January 15, 2010
概括
调节性T (Treg) 细胞种群是由Foxp3位点的保存的非编码DNA元素 (CNS) 控制的. 这些中枢神经系统元素决定Treg细胞的大小,组成和稳定性,确保免疫恒常.
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:
- 免疫平衡依赖于调节性T (Treg) 细胞来控制免疫反应.
- 特雷格细胞对转录因子Foxp3进行上调,以实现血统结合,无论是在胸腺 (tTreg) 或外围 (iTreg).
- 在Foxp3位点保存的非编码序列 (CNS) 被假设为调节Treg细胞群体动态.
研究的目的:
- 为了研究在小鼠Treg细胞命运决定中三个Foxp3中枢神经系统元素 (CNS1-3) 的功能.
- 了解这些中枢神经系统元素如何控制Treg细胞群体的大小,组成和稳定性.
主要方法:
- 在体外结合测试以确定与中枢神经系统元素的蛋白质相互作用.
- 在有针对性中枢神经系统修改的小鼠模型中分析Treg细胞分化和功能.
- 研究DNA脱甲基化和转录因子结合在中枢神经系统功能中的作用.
主要成果:
- 中枢神经系统3作为一个先驱元素,显著增加了胸腺和外围Treg细胞的频率,并结合c-Rel.
- 含有TGF-β-NFAT反应元件的CNS1,对于肠关联淋巴细胞组织中的iTreg细胞生成至关重要,但不对tTreg分化至关重要.
- CNS2对于维持Foxp3表达在分裂的Treg细胞后代中至关重要,涉及Foxp3以脱甲基化依赖的方式结合,这表明它在血统稳定性中的作用.
结论:
- 福克斯p3 中枢神经系统元素在响应特定的线索时差异调节Treg细胞的生成和维护.
- 中枢神经系统3促进Treg细胞的产生,中枢神经系统1是外围Treg诱导的关键,中枢神经系统2通过遗传性表观遗传记忆确保血统稳定.
- 这些发现揭示了Foxp3位点的一个复杂的调节网络,控制了Treg细胞群体动态,以实现免疫平衡.
相关概念视频
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The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...