美国梅奥诊所免疫学系Khashayarsha Khazaie、美国芝加哥大学Fotini Gounari以及美国普渡大学Majid Kazemian研究团队合作取得最新进展。TCF-1 控制调节炎症、CD8 + T 细胞细胞毒性和结肠癌严重程度的调节性 T (Treg)细胞功能。相关论文于2021年8月12日发表在《自然—免疫学》杂志上。

他们表明 TCF-1 主要抑制由 Foxp3 共同结合基因的转录。单细胞 RNA 测序分析鉴定了效应记忆 T 细胞和中央记忆 Treg 细胞，它们具有 Klf2 和记忆和激活标记的差异表达。 TCF-1 缺乏并没有改变核心 Treg 细胞转录特征，但促进了替代信号通路，从而 Treg 细胞被激活并获得了辅助 T 细胞 TH17 亚群的肠道归巢特性和特征。TCF-1 缺陷的 Treg 细胞强烈抑制 T 细胞增殖和细胞毒性，但在控制 CD4 + T 细胞极化和炎症方面受到损害。

在患有息肉病的小鼠中，Treg 细胞特异性 TCF-1 缺乏促进了肿瘤生长。与邻近的正常组织和循环 T 细胞相比，结直肠癌患者的肿瘤浸润性 Treg 细胞表现出较低的 TCF-1 表达和增加的 TH17 表达特征。因此，Treg 细胞特异性 TCF-1 表达差异调节 TH17 介导的炎症和 T 细胞细胞毒性，并可确定结直肠癌预后。

据介绍，转录因子 TCF-1 对Treg细胞的发育和功能至关重要；然而，人们对其功能知之甚少。

附：英文原文

Title: TCF-1 controls Treg cell functions that regulate inflammation, CD8+ T cell cytotoxicity and severity of colon cancer

Author: Osman, Abu, Yan, Bingyu, Li, Ying, Pavelko, Kevin D., Quandt, Jasmine, Saadalla, Abdulrahman, Singh, Mahendra Pal, Kazemian, Majid, Gounari, Fotini, Khazaie, Khashayarsha

Issue&Volume: 2021-08-12

Abstract: 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.

DOI: 10.1038/s41590-021-00987-1

Source: https://www.nature.com/articles/s41590-021-00987-1