Polyamine synthesis represents one of the most profound metabolic changes during T cell activation, but the biological implications of this are scarcely known. Here, we show that polyamine metabolism is a fundamental process governing the ability of CD4⁺ helper T cells (T_H) to polarize into different functional fates. Deficiency in ornithine decarboxylase, a crucial enzyme for polyamine synthesis, results in a severe failure of CD4⁺ T cells to adopt correct subset specification, underscored by ectopic expression of multiple cytokines and lineage-defining transcription factors across T_H cell subsets. Polyamines control T_H differentiation by providing substrates for deoxyhypusine synthase, which synthesizes the amino acid hypusine, and mice in which T cells are deficient for hypusine develop severe intestinal inflammatory disease. Polyamine-hypusine deficiency caused widespread epigenetic remodeling driven by alterations in histone acetylation and a re-wired tricarboxylic acid (TCA) cycle. Thus, polyamine metabolism is critical for maintaining the epigenome to focus T_H cell subset fidelity.

多胺合成代表了 T 细胞活化过程中最深刻的代谢变化之一，但其生物学意义鲜为人知。在这里，我们表明多胺代谢是控制 CD4 ⁺辅助 T 细胞 (T _H ) 极化成不同功能命运的能力的基本过程。鸟氨酸脱羧酶是多胺合成的关键酶，缺乏鸟氨酸脱羧酶会导致 CD4 ^{+ T 细胞严重无法采用正确的亚群规范，这通过 T} _H细胞亚群中多种细胞因子和谱系定义转录因子的异位表达来强调。多胺控制 T _H通过为合成氨基酸hypusine的脱氧hypusine合酶提供底物进行分化，并且T细胞缺乏hypusine的小鼠会发展为严重的肠道炎症性疾病。多胺 - hypusine 缺乏导致广泛的表观遗传重塑，由组蛋白乙酰化和重新连接的三羧酸 (TCA) 循环的改变驱动。因此，多胺代谢对于维持表观基因组以聚焦 T _H细胞亚群保真度至关重要。