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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Puleston, DJ; Baixauli, F; Sanin, DE; Edwards-Hicks, J; Villa, M; Kabat, AM; Kaminski, MM; Stanckzak, M; Weiss, HJ; Grzes, KM; Piletic, K; Field, CS; Corrado, M; Haessler, F; Wang, C; Musa, Y; Schimmelpfennig, L; Flachsmann, L; Mittler, G; Yosef, N; Kuchroo, VK; Buescher, JM; Balabanov, S; Pearce, EJ; Green, DR; Pearce, EL.
Polyamine metabolism is a central determinant of helper T cell lineage fidelity
CELL. 2021; 184(16): 4186-+.
Doi: 10.1016/j.cell.2021.06.007
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- Villa Matteo
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- Abstract:
- 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.