Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305-5166, USA.
Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94304, USA.
Int J Mol Sci. 2020 Sep 5;21(18):6497. doi: 10.3390/ijms21186497.
The transcription factor T cell factor 1 (TCF1), a pioneer transcription factor as well as a downstream effector of WNT/β-catenin signaling, is indispensable for T cell development in the thymus. Recent studies have highlighted the additional critical role of TCF1 in peripheral T cell responses to acute and chronic infections as well as cancer. Here, we review the regulatory functions of TCF1 in the differentiation of T follicular helper cells, memory T cells and recently described stem-like exhausted T cells, where TCF1 promotes less differentiated stem-like cell states by controlling common gene-regulatory networks. These studies also provide insights into the mechanisms of defective T cell responses in older individuals. We discuss alterations in TCF1 expression and related regulatory networks with age and their consequences for T cell responses to infections and vaccination. The increasing understanding of the pathways regulating TCF1 expression and function in aged T cells holds the promise of enabling the design of therapeutic interventions aiming at improving T cell responses in older individuals.
转录因子 T 细胞因子 1（TCF1）既是先驱转录因子，也是 WNT/β-连环蛋白信号的下游效应因子，对于胸腺中的 T 细胞发育是不可或缺的。最近的研究强调了 TCF1 在急性和慢性感染以及癌症中对周围 T 细胞反应的额外关键作用。在这里，我们回顾了 TCF1 在 T 滤泡辅助细胞、记忆 T 细胞和最近描述的干细胞样耗竭 T 细胞分化中的调节功能，其中 TCF1 通过控制共同的基因调控网络促进分化程度较低的干细胞样细胞状态。这些研究还为年龄较大个体中 T 细胞反应缺陷的机制提供了新的见解。我们讨论了 TCF1 表达和相关调控网络随年龄的变化及其对感染和疫苗接种时 T 细胞反应的影响。越来越多的关于调节衰老 T 细胞中 TCF1 表达和功能的途径的理解，为设计旨在改善年龄较大个体 T 细胞反应的治疗干预措施提供了希望。
