Barbi Joseph, Pardoll Drew, Pan Fan
Department of Oncology, Immunology and Hematopoiesis Division, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Immunol Rev. 2014 May;259(1):115-39. doi: 10.1111/imr.12172.
Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3(+) Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3(+) Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting, and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability.
调节性T细胞（Tregs）通过其抑制功能预防自身免疫以及过度或不必要的免疫激活所导致的组织损伤。虽然它们对正常免疫控制的重要性不可否认，但Treg谱系的稳定性最近已成为一个有争议的话题。许多报告显示，在各种炎症条件下，标志性的Treg转录因子叉头框蛋白3（Foxp3）和Treg功能会显著丧失。其他近期研究表明，大多数Tregs在Foxp3表达和抑制功能保留方面具有极强的弹性。虽然这场争论在近期不太可能得到解决，但更好地理解Foxp3(+) Treg群体内相当大的异质性以及Treg亚群如何应对不同的环境线索可能是调和的关键。在这篇综述中，我们讨论了导致观察到的Foxp3(+) Treg身份和功能稳定性或不稳定性的多种机制。这些机制包括转录和表观遗传程序、转录本靶向以及似乎对微环境的众多因素有反应的翻译后修饰。这些Treg功能调节机制进一步丰富了关于Treg稳定性的讨论。
