Vent-Schmidt Jens, Han Jonathan M, MacDonald Katherine G, Levings Megan K
Department of Surgery, University of British Columbia and Child & Family Research Institute , Vancouver, British Columbia , Canada.
Int Rev Immunol. 2014 Mar;33(2):110-28. doi: 10.3109/08830185.2013.811657. Epub 2013 Aug 15.
Regulatory T cells (Tregs) act in trans to control immune responses. The suppressive function of Tregs relies heavily on high and stable expression of the transcription factor FOXP3, which, together with other transcription factors, activates anti-inflammatory genes and represses proinflammatory genes. FOXP3 is required to shape the unique signaling mechanisms in Tregs, creating a positive-feedback pathway to further enhance its own expression. In addition, FOXP3 is thought to switch on a complex transcriptional network that leads to the stabilization of the Treg phenotype. Emerging data reveal that FOXP3 achieves this function in concert with several other transcription factors, many of which are associated with lineages of conventional T cells. In this review, we will discuss the structural features of FOXP3 and how it functions by interacting with other transcription factors. We will also summarize the role of FOXP3 in establishing the unique signaling cascades in Tregs. Finally, we will dissect the cooperative roles of FOXP3 and other T-cell lineage-defining transcription factors and discuss how these networks not only control the ability to Tregs to suppress different types of immune responses, but also enable Treg plasticity.
调节性T细胞（Tregs）通过反式作用来控制免疫反应。Tregs的抑制功能严重依赖于转录因子FOXP3的高表达和稳定表达，FOXP3与其他转录因子一起激活抗炎基因并抑制促炎基因。FOXP3是塑造Tregs中独特信号机制所必需的，它创建了一个正反馈途径以进一步增强其自身表达。此外，FOXP3被认为开启了一个复杂的转录网络，该网络导致Treg表型的稳定。新出现的数据表明，FOXP3与其他几个转录因子协同发挥这一功能，其中许多转录因子与传统T细胞谱系相关。在这篇综述中，我们将讨论FOXP3的结构特征以及它如何通过与其他转录因子相互作用发挥功能。我们还将总结FOXP3在建立Tregs中独特信号级联反应中的作用。最后，我们将剖析FOXP3与其他T细胞谱系定义转录因子的协同作用，并讨论这些网络如何不仅控制Tregs抑制不同类型免疫反应的能力，还能使Treg具有可塑性。
