Transcriptional and epigenetic networks of helper T and innate lymphoid cells.
Transcriptional and epigenetic networks of helper T and innate lymphoid cells.
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DOI：
10.1111/imr.12208
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发表时间：
2014-09
影响因子：
8.7
通讯作者：
O'Shea JJ
中科院分区：
文献类型：
--
作者：
Shih HY;Sciumè G;Poholek AC;Vahedi G;Hirahara K;Villarino AV;Bonelli M;Bosselut R;Kanno Y;Muljo SA;O'Shea JJ
CD4+辅助性T细胞特异性分化为离散效应细胞“谱系”的发现，代表了宿主防御和免疫调节机制概念化的分水岭事件。然而，我们对辅助性T细胞亚群的实际复杂性的认识有增无减。就像斯堪的纳维亚的萨米语有1000个不同的驯鹿单词一样，CD4+ T细胞的命运范围是众多的，可能被低估了。在辅助性T细胞亚群的拥挤场景中增加的是先天淋巴样细胞（ILC）的不断增长的家族，其被赋予共同的效应子应答，并且先前定义的用于CD4+辅助性T细胞亚群的“主调节因子”也由ILC亚群共享。在这种异常复杂的背景下，转录组和表观基因组的理解也随之取得了进展。那么，在世纪初，“谱系承诺”和辅助性T细胞“特化”等术语意味着什么呢？我们如何将所有这些放在一个连贯的概念框架中？如果认为我们已经有了足够复杂的理解来认真回答这些问题，那将是傲慢的。相反，我们将审查目前状态的灵活性辅助T细胞反应的基因调控网络和表观遗传景观。最近的数据提供了重大的惊喜，关于主调节因子可以或不能做什么，它们如何与其他转录因子相互作用并影响全球基因组范围的变化，以及所有这些因素如何共同影响辅助细胞功能。
The discovery of the specification of CD4+ helper T cells to discrete effector “lineages” represented a watershed event in conceptualizing mechanisms of host defense and immunoregulation. However, our appreciation for the actual complexity of helper T cell subsets continues unabated. Just as the Sami language of Scandinavia has 1000 different words for reindeer, the range of fates available for a CD4+ T cell is numerous and may be underestimated. Added to the crowded scene for helper T cell subsets is the continuously growing family of innate lymphoid cells (ILCs), endowed with common effector responses and the previously defined “master regulators” for CD4+ helper T cell subsets are also shared by ILC subsets. Within the context of this extraordinary complexity are concomitant advances in the understanding of transcriptomes and epigenomes. So what do terms like “lineage commitment” and helper T cell “specification” mean in the early 21st century? How do we put all of this together in a coherent conceptual framework? It would be arrogant to assume that we have a sophisticated enough understanding to seriously answer these questions. Instead, we will review the current status of the flexibility of helper T cell responses in relation to their genetic regulatory networks and epigenetic landscapes. Recent data have provided major surprises as to what master regulators can or cannot do, how they interact with other transcription factors and impact global genome-wide changes and how all these factors come together to influence helper cell function.