Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Curr Top Microbiol Immunol. 2012;356:145-64. doi: 10.1007/82_2011_141.
It is currently unclear whether our classifications for T helper cell subtypes truly define stable lineages or rather they represent cells with a more flexible phenotype. This distinction is important for predicting the behavior of T helper cells during normal immune responses as well as in pathogenic conditions. Determining the mechanisms by which T helper cell lineage-defining transcription factors are expressed and subsequently regulate epigenetic and downstream gene regulatory events will provide insight into this complex question. Importantly, lineage-defining transcription factors that regulate epigenetic events have the potential to redefine the fate of the cell when they are expressed. In contrast, factors that regulate the events downstream of a permissive epigenetic environment will only have the capacity to modulate the underlying gene expression profile that is already established in that cell. Finally, mechanisms related to the antagonism versus cooperation between the lineage-defining factors for opposing T helper cell subsets will influence the characteristics of the cell. Here, we provide an overview of these topics by discussing epigenetic states in T helper cell subtypes as well as the mechanisms by which lineage-defining factors, such as T-bet, regulate gene expression profiles at both the epigenetic and general transcription level. We also examine some of what is known about the interplay between the T helper cell lineage-defining transcription factors T-bet, GATA3, Foxp3, Rorγt, and Bcl-6 and how this relates to the proper functioning of T helper cell subsets. Defining the mechanisms by which these factors regulate gene expression profiles will aid in our ability to predict the functional capabilities of T helper cell subsets.
目前尚不清楚我们对辅助性 T 细胞亚型的分类是否真正定义了稳定的谱系，或者它们是否代表了具有更灵活表型的细胞。这种区别对于预测辅助性 T 细胞在正常免疫反应以及致病条件下的行为很重要。确定辅助性 T 细胞谱系定义转录因子表达的机制，以及随后调节表观遗传和下游基因调控事件，将为解决这个复杂问题提供线索。重要的是，调节表观遗传事件的谱系定义转录因子在表达时有可能重新定义细胞的命运。相比之下，调节允许的表观遗传环境下游事件的因子仅具有调节该细胞中已经建立的潜在基因表达谱的能力。最后，与拮抗或合作相关的机制在相反的辅助性 T 细胞亚群的谱系定义因子之间，将影响细胞的特征。在这里，我们通过讨论辅助性 T 细胞亚型中的表观遗传状态以及 T 细胞谱系定义因子（如 T-bet）在表观遗传和一般转录水平上调节基因表达谱的机制，来概述这些主题。我们还研究了一些已知的关于辅助性 T 细胞谱系定义转录因子 T-bet、GATA3、Foxp3、Rorγt 和 Bcl-6 之间的相互作用，以及这与辅助性 T 细胞亚群的正常功能有何关系。定义这些因子调节基因表达谱的机制将有助于我们预测辅助性 T 细胞亚群的功能能力。
