马克斯·普朗克免疫生物学和表观遗传学研究所Erika L. Pearce课题组发现，多胺代谢是辅助T细胞谱系保真度的核心决定因素。该研究于2021年7月2日在线发表于国际一流学术期刊《细胞》。
研究人员表明，多胺代谢是控制CD4+辅助T细胞（TH）极化为不同功能命运的能力的基本过程。鸟氨酸脱羧酶（多胺合成的一种关键酶）的缺乏导致CD4+ T细胞严重无法实现正确的亚群特化，多种细胞因子和跨TH细胞亚群的谱系定义转录因子的异位表达强调了这一点。多胺通过为合成氨基酸（hypusine）的脱氧hypusine合酶提供底物来控制TH分化，而其中T细胞缺乏hypusine的小鼠会发展为严重的肠道炎症。
多胺-hypusine缺乏导致广泛的表观遗传重塑，这是由组蛋白乙酰化的改变和重塑的三羧酸（TCA）循环驱动的。因此，多胺代谢对于维持表观基因组从而确保TH细胞亚群保真度至关重要。
据悉，多胺合成是T细胞活化过程中最深刻的代谢变化之一，但其生物学意义尚不清楚。
附：英文原文
Title: Polyamine metabolism is a central determinant of helper T cell lineage fidelity
Author: Daniel J. Puleston, Francesc Baixauli, David E. Sanin, Joy Edwards-Hicks, Matteo Villa, Agnieszka M. Kabat, Marcin M. Kamiński, Michal Stanckzak, Hauke J. Weiss, Katarzyna M. Grzes, Klara Piletic, Cameron S. Field, Mauro Corrado, Fabian Haessler, Chao Wang, Yaarub Musa, Lena Schimmelpfennig, Lea Flachsmann, Gerhard Mittler, Nir Yosef, Vijay K. Kuchroo, Joerg M. Buescher, Stefan Balabanov, Edward J. Pearce, Douglas R. Green, Erika L. Pearce
Issue&Volume: 2021-07-02
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 (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.
DOI: 10.1016/j.cell.2021.06.007
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00708-X