The ability of the immune system to discriminate external stimuli from self-components – namely immune tolerance – occurs through a coordinated cascade of events involving a dense network of immune cells. Among them, CD4⁺CD25⁺ T regulatory cells are crucial to balance immune homeostasis and function. Growing evidence supports the notion that energy metabolites can dictate T cell fate and function via epigenetic modifications, which affect gene expression without altering the DNA sequence. Moreover, changes in cellular metabolism couple with activation of immune pathways and epigenetic remodeling to finely tune the balance between T cell activation and tolerance. This Review summarizes these aspects and critically evaluates novel possibilities for developing therapeutic strategies to modulate immune tolerance through metabolism via epigenetic drugs.

免疫系统将外部刺激与自身成分区分开来的能力——即免疫耐受——是通过涉及密集免疫细胞网络的一系列事件协调发生的。其中，CD4 ⁺ CD25 ⁺T 调节细胞对于平衡免疫稳态和功能至关重要。越来越多的证据支持这样一种观点，即能量代谢物可以通过表观遗传修饰决定 T 细胞的命运和功能，这会影响基因表达而不改变 DNA 序列。此外，细胞代谢的变化与免疫途径的激活和表观遗传重塑相结合，以微调 T 细胞激活和耐受性之间的平衡。本综述总结了这些方面，并批判性地评估了开发通过表观遗传药物代谢来调节免疫耐受的治疗策略的新可能性。