时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
While individual BCAAs have unique roles in organismal and cellular physiology, the mechanisms underlying their individual effects remain poorly understood.；In contrast, direct sensors or even direct downstream molecular mechanisms for Val-regulated biology remain unknown.；However, the precise molecular mechanisms explaining how each of these components cross-talk and reinforce one another remain a key knowledge gap.
方法
Results Leucine is dispensable for T cell cycle entry and proliferation To investigate the role of each of the BCAAs in T cell biology, we assayed the impact of BCAA restriction on cycle entry, activation, proliferation and function of activated primary CD8 T cells.；Bulk CD8 T cells were isolated and purified from spleens of WT mice, activated with anti-CD3 and anti-CD28 antibodies (2 ug/mL each) for 2 days in replete TCM followed by 2 days in BCAA-free TCM with addback of varying combinations of Leu, Ile and Val (0.8 mM or 2.4 mM [3X] each as indicated).；(C) includes data from two independent experiments, each with 2–3 technical replicates, and phenotype also repeats with CD25+ staining in experiments in Fig.；Phenotype also repeats with Ki67hi or Ki67hi /DAPIlo staining in experiments in Figs. 4B and EV5D.
核心结论
We demonstrate that the three BCAAs have distinct roles in T cell biology.；Together, we find that the discrete sensing of the BCAAs uncouples two major anabolic reg- ulators, mTORC1 and c-Myc, in cell growth.；In contrast, direct sensors or even direct downstream molecular mechanisms for Val-regulated biology remain unknown. ‖ 结论：Altogether, our work supports a model in which CD8 T cells can sustain their core programming through discrete modules that vary in their nutrient sensitivity.
局限
Beyond activation, our analysis revealed that extracellular Val is sufficient to support cytokine production, despite the lack of proliferation in these cultures (Fig.；Future studies will need to clarify how T cells integrate signals from both mTORC1 and Figure 4.；Of note, our data in early quiescence exit or the partial rescue of proliferation by rapamycin, also indicate that the exacerbation of nutrient stress by Leu-mTORC1-driven metabolic demand may not be the only mechanism at play.
对本项目的价值
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全文来源
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原文题录
- 英文标题：Distinct sensing of BCAAs by mTOR and c-Myc governs T cell proliferation, independent of catabolism.
- 期刊与标识：EMBO Rep · PMID 42957880 · DOI 10.1038/s44319-026-00919-w
B 级证据分级：B 级（同行评议临床前研究，主要为动物模型）
本文核心结论来自动物模型或体外细胞学，属临床前证据，不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义，与人类临床结局之间仍有距离。
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