调节性T细胞中的CRISPR屏幕显示了Foxp3的调节器
Jessica T Cortez1,2,3,4, Elena Montauti5, Eric Shifrut2,3,4
1Biomedical Sciences Graduate Program, University of California, San Francisco, CA, USA.
Nature
|June 6, 2020
概括
研究人员确定了Foxp3的关键调节剂,Foxp3是调节性T (Treg) 细胞至关重要的蛋白质. Usp22稳定了Foxp3,而Rnf20则使其不稳定,为癌症和自身免疫性疾病的免疫疗法提供了新的点.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 调节性T (Treg) 细胞对于免疫平衡至关重要,但阻碍抗瘤免疫力.
- 标志着Foxp3损失的Treg不稳定性可以驱动自身免疫或增强抗瘤反应.
- 了解Foxp3调节对于开发基于Treg的癌症和自身免疫性疾病疗法至关重要.
研究的目的:
- 在小鼠Treg细胞中识别控制Foxp3表达的基因调节程序.
- 在癌症和自身免疫性疾病中发现调节Treg细胞功能的新目标.
主要方法:
- 开发了基于CRISPR的Treg细胞表型组平台.
- 执行了大约500个核因子的目标功能损失选.
- 研究了USP22和Rnf20在Treg细胞功能和稳定性中的作用.
主要成果:
- 鉴定出基因特异性酶22 (Usp22) 作为稳定Foxp3表达的积极调节剂.
- 确定了环指蛋白20 (Rnf20) 作为Foxp3表达的负调节剂.
- Treg 特定的 Usp22 切除导致自身免疫力和抗瘤免疫力受损,而 Rnf20 切除则可挽回,这表明存在互惠的泛素切换.
结论:
- 发现了Foxp3,Usp22和Rnf20的新型调节剂,突出了基于无处不在的调节机制.
- 在初级Treg细胞中展示了功能基因组学的强大的CRISPR选平台.
- 这些发现为开发用于癌症和自身免疫性疾病的Treg免疫疗法提供了新的点.
相关概念视频
CRISPR
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...
CRISPR
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...
Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...


