细胞毒性T细胞
FOXP3型
T细胞
炎症
生物
癌症研究
转录因子
CD8型
细胞
细胞生物学
免疫学
免疫系统
基因
体外
遗传学
生物化学
作者
Abu Osman,Bingyu Yan,Ying Liu,Kevin D. Pavelko,Jasmine Quandt,Abdulrahman Saadalla,Mahendra Singh,Majid Kazemian,Fotini Gounari,Khashayarsha Khazaie
标识
DOI:10.1038/s41590-021-00987-1
摘要
The transcription factor TCF-1 is essential for the development and function of regulatory T (Treg) cells; however, its function is poorly understood. Here, we show that TCF-1 primarily suppresses transcription of genes that are co-bound by Foxp3. Single-cell RNA-sequencing analysis identified effector memory T cells and central memory Treg cells with differential expression of Klf2 and memory and activation markers. TCF-1 deficiency did not change the core Treg cell transcriptional signature, but promoted alternative signaling pathways whereby Treg cells became activated and gained gut-homing properties and characteristics of the TH17 subset of helper T cells. TCF-1-deficient Treg cells strongly suppressed T cell proliferation and cytotoxicity, but were compromised in controlling CD4+ T cell polarization and inflammation. In mice with polyposis, Treg cell-specific TCF-1 deficiency promoted tumor growth. Consistently, tumor-infiltrating Treg cells of patients with colorectal cancer showed lower TCF-1 expression and increased TH17 expression signatures compared to adjacent normal tissue and circulating T cells. Thus, Treg cell-specific TCF-1 expression differentially regulates TH17-mediated inflammation and T cell cytotoxicity, and can determine colorectal cancer outcome.
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