Department of Microbiology, University of Alabama at Birmingham, Alabama 35294, USA; email:
Annu Rev Immunol. 2018 Apr 26;36:221-246. doi: 10.1146/annurev-immunol-042617-053127. Epub 2018 Jan 12.
Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications. We discuss this topic from the perspective of specialized CD4 T cells as well as effector and memory T cell differentiation programs. We also highlight findings from embryonic stem cells that give mechanistic insight into how nutrients processed through pathways such as glycolysis, glutaminolysis, and one-carbon metabolism regulate metabolite levels to influence epigenetic events and discuss similar mechanistic principles in T cells. Finally, we highlight how dysregulated environments, such as the tumor microenvironment, might alter programming events.
研究人员正在加紧努力，以了解代谢状态变化影响分化程序的机制。一个新的目标是定义代谢物的波动如何影响促成分化程序的表观遗传状态。这是因为代谢物，如 S-腺苷甲硫氨酸、乙酰辅酶 A、α-酮戊二酸、2-羟基戊二酸和丁酸盐，是表观遗传修饰复合物和表观遗传修饰的供体、底物、辅因子和拮抗剂。我们从专门的 CD4 T 细胞以及效应器和记忆 T 细胞分化程序的角度讨论这个话题。我们还强调了胚胎干细胞的发现，这些发现为营养物质通过糖酵解、谷氨酰胺分解和一碳代谢等途径加工如何调节代谢物水平以影响表观遗传事件提供了机制上的见解，并讨论了 T 细胞中类似的机制原则。最后，我们强调了失调的环境，如肿瘤微环境，如何改变编程事件。
