| First Author | Puleston DJ | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 16 | Pages | 4186-4202.e20 |
| PubMed ID | 34216540 | Mgi Jnum | J:310078 |
| Mgi Id | MGI:6756282 | Doi | 10.1016/j.cell.2021.06.007 |
| Citation | Puleston DJ, et al. (2021) Polyamine metabolism is a central determinant of helper T cell lineage fidelity. Cell 184(16):4186-4202.e20 |
| abstractText | 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 (TH) 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 TH cell subsets. Polyamines control TH 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 TH cell subset fidelity. |
