Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.
Departments of Biochemistry and Computer Science, Purdue University, West Lafayette, IN, USA.
Nat Rev Immunol. 2023 Dec;23(12):842-856. doi: 10.1038/s41577-023-00893-7. Epub 2023 Jun 19.
Forkhead box protein 3-expressing (FOXP3) regulatory T cells (T cells) suppress conventional T cells and are essential for immunological tolerance. FOXP3, the master transcription factor of T cells, controls the expression of multiples genes to guide T cell differentiation and function. However, only a small fraction (<10%) of T cell-associated genes are directly bound by FOXP3, and FOXP3 alone is insufficient to fully specify the T cell programme, indicating a role for other accessory transcription factors operating upstream, downstream and/or concurrently with FOXP3 to direct T cell specification and specialized functions. Indeed, the heterogeneity of T cells can be at least partially attributed to differential expression of transcription factors that fine-tune their trafficking, survival and functional properties, some of which are niche-specific. In this Review, we discuss the emerging roles of accessory transcription factors in controlling T cell identity. We specifically focus on members of the basic helix-loop-helix family (AHR), basic leucine zipper family (BACH2, NFIL3 and BATF), CUT homeobox family (SATB1), zinc-finger domain family (BLIMP1, Ikaros and BCL-11B) and interferon regulatory factor family (IRF4), as well as lineage-defining transcription factors (T-bet, GATA3, RORγt and BCL-6). Understanding the imprinting of T cell identity and specialized function will be key to unravelling basic mechanisms of autoimmunity and identifying novel targets for drug development.
叉头框蛋白 3 表达（FOXP3）调节性 T 细胞（T 细胞）抑制常规 T 细胞，是免疫耐受的关键。FOXP3 是 T 细胞的主要转录因子，控制着多种基因的表达，指导 T 细胞分化和功能。然而，只有一小部分（<10%）与 T 细胞相关的基因直接被 FOXP3 结合，而且 FOXP3 本身不足以完全指定 T 细胞的程序，这表明其他辅助转录因子在 FOXP3 上游、下游和/或同时发挥作用，以指导 T 细胞的特化和特化功能。事实上，T 细胞的异质性至少部分归因于转录因子的差异表达，这些转录因子微调了它们的运输、存活和功能特性，其中一些是特定于生态位的。在这篇综述中，我们讨论了辅助转录因子在控制 T 细胞特性方面的新作用。我们特别关注基本螺旋-环-螺旋家族（AHR）、碱性亮氨酸拉链家族（BACH2、NFIL3 和 BATF）、CUT 同源盒家族（SATB1）、锌指结构域家族（BLIMP1、Ikaros 和 BCL-11B）和干扰素调节因子家族（IRF4），以及谱系定义转录因子（T-bet、GATA3、RORγt 和 BCL-6）。了解 T 细胞特性和特化功能的印记将是揭示自身免疫基本机制和确定新药开发新靶点的关键。
