Cell子刊:限制甲硫氨酸摄入或可治疗自身免疫疾病
创作:szx 审核:szx 03月01日
  • 代谢组学分析显示,活化T细胞可快速摄取甲硫氨酸,并将后者作为S-腺苷-L-甲硫氨酸(SAM,可作为通用的甲基供体)的主要合成底物;
  • 限制甲硫氨酸可减少T细胞内的SAM水平;
  • 在Th17细胞中,限制甲硫氨酸可在细胞增殖及细胞因子产生的关键基因的启动子区域降低组蛋白H3K4的甲基化,以抑制Th17细胞的扩增;
  • 在实验性自身免疫性脑脊髓炎小鼠模型中,限制甲硫氨酸的摄入可减少致病性Th17细胞的扩增,以缓解T细胞介导的神经炎症。
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szx
Cell Metabolism上发表的一项最新研究,报道了饮食中的甲硫氨酸调控T细胞应答的机制:活化T细胞可快速摄取甲硫氨酸,将其作为甲基供体——S-腺苷-L-甲硫氨酸(SAM)的合成底物。在Th17细胞中,限制甲硫氨酸可减少细胞内的SAM,以抑制关键基因的启动子的组蛋白甲基化修饰,从而抑制Th17细胞的扩增。在自身免疫疾病小鼠模型中,限制甲硫氨酸的摄入可抑制T细胞介导的神经炎症。结果提示,调节饮食中的甲硫氨酸摄入或可作为治疗自身免疫疾病的策略。
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Cell Metabolism [IF:21.567]

Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming

甲硫氨酸代谢通过调控表观遗传以影响Th细胞应答

10.1016/j.cmet.2020.01.006

02-04, Article

Abstract & Authors:展开

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Epigenetic modifications on DNA and histones regulate gene expression by modulating chromatin accessibility to transcription machinery. Here we identify methionine as a key nutrient affecting epigenetic reprogramming in CD4 + T helper (Th) cells. Using metabolomics, we showed that methionine is rapidly taken up by activated T cells and serves as the major substrate for biosynthesis of the universal methyl donor S-adenosyl-L-methionine (SAM). Methionine was required to maintain intracellular SAM pools in T cells. Methionine restriction reduced histone H3K4 methylation (H3K4me3) at the promoter regions of key genes involved in Th17 cell proliferation and cytokine production. Applied to the mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis), dietary methionine restriction reduced the expansion of pathogenic Th17 cells in vivo, leading to reduced T cell-mediated neuroinflammation and disease onset. Our data identify methionine as a key nutritional factor shaping Th cell proliferation and function in part through regulation of histone methylation.

First Authors:
Dominic G Roy,Jocelyn Chen

Correspondence Authors:
Russell G Jones

All Authors:
Dominic G Roy,Jocelyn Chen,Victoria Mamane,Eric H Ma,Brejnev M Muhire,Ryan D Sheldon,Tatiana Shorstova,Rutger Koning,Radia M Johnson,Ekaterina Esaulova,Kelsey S Williams,Sebastian Hayes,Mya Steadman,Bozena Samborska,Amanda Swain,Audrey Daigneault,Victor Chubukov,Thomas P Roddy,William Foulkes,J Andrew Pospisilik,Marie-Claude Bourgeois-Daigneault,Maxim N Artyomov,Michael Witcher,Connie M Krawczyk,Catherine Larochelle,Russell G Jones

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