Polyamine metabolism is a central determinant of helper T cell lineage fidelity

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.

Automated summary

Polyamine synthesis plays a critical role in T cell activation and differentiation, regulating CD4(+) T cells' function and epigenetic remodeling. Studies have revealed the significance of polyamine metabolism in controlling the fate of T-H cell subsets, with deficiency leading to aberrant expression of cytokines and transcription factors.