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Immunobiology. 2025 Jun 7;230(4):153087. doi: 10.1016/j.imbio.2025.153087 Q42.52024

Integrated transcriptomic, metabolomic, and lipidomic analyses reveal a unique lipid profile of regulatory T cells upon activation

整合转录组、代谢组和脂质组分析揭示激活后调节性T细胞独特的脂质特征 翻译改进

Yohei Sato  1, Misa Yura  2, Alana Chandler  2, Yamato Hanawa  2, Akihito Tsubota  3

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作者单位

  • 1 Laboratory of Immune Cell Therapy, Project Research Units, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Core Research Facility, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Immunology and Allergy Research Unit, Division of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. Electronic address: yoheisato@jikei.ac.jp.
  • 2 Laboratory of Immune Cell Therapy, Project Research Units, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
  • 3 Project Research Units, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.

    • DOI: 10.1016/j.imbio.2025.153087 PMID: 40499231

    摘要 中英对照阅读

    Regulatory T cells (Tregs) exhibit stable FOXP3 expression and regulate the immune response through suppressive activity. Their unique metabolic properties include increased glycolysis and oxidative phosphorylation. We combined transcriptomic, metabolomic, and lipidomic analyses to dissect the metabolic dynamics of Tregs upon activation. Combined metabolomic and lipidomic analyses showed that freshly isolated and activated Tregs had distinct metabolomic and lipidomic properties, respectively. Compared with activated effector T cells (Teffs), activated Tregs contained omega-3 long-chain polyunsaturated fatty acid (PUFA)-rich diglycerides and triglycerides. These were supported by transcriptomics data, showing upregulation of PPAR-alpha and PPAR-gamma. Compared with activated Teffs, activated Tregs exhibited greater ceramide production, consistent with the upregulation of ceramide synthase and sphingomyelin synthase. Confocal microscopy revealed that Tregs, in contrast to Teffs, were enriched in lysosomes and peroxisomes upon activation. Our data confirm the unique metabolic properties of Tregs, especially those characterized by omega-3 long-chain PUFA-rich triglycerides and ceramides, together with enriched lysosomes and peroxisomes, which correspond to metabolic alterations.

    Keywords: FOXP3; Lipidomics; Lysosome; Metabolomics; Omega-3 long-chain polyunsaturated fatty acids; PPAR-gamma; Peroxisome; RRAR-alpha; Regulatory T cells; Triglyceride.

    Keywords：integrated transcriptomic; metabolomic; lipidomic analyses; regulatory t cells; activation

    调节性T细胞（Tregs）表现出稳定的FOXP3表达，并通过抑制活性调控免疫反应。它们独特的代谢特性包括增强的糖酵解和氧化磷酸化。我们结合转录组学、代谢组学和脂质组学分析，剖析了活化后Tregs的代谢动力学。结合代谢组学和脂质组学分析显示，新鲜分离的和激活的Tregs具有不同的代谢组学和脂质组学特性。与激活的效应T细胞（Teffs）相比，激活的Tregs含有富含ω-3长链多不饱和脂肪酸（PUFA）的二酰基甘油和三酰基甘油。这些结果得到了转录组数据的支持，显示PPAR-alpha 和 PPAR-gamma 的上调。与激活的Teffs相比，激活的Tregs表现出更大的鞘氨醇生产量，这与其鞘氨醇合成酶和鞘磷脂合成酶的上调一致。共聚焦显微镜观察发现，在活化过程中，Tregs相对于Teffs富含溶酶体和过氧化物酶体。我们的数据证实了Tregs的独特代谢特性，尤其是那些以富含ω-3长链PUFA的三酰基甘油和鞘氨醇为特征，并且富含溶酶体和过氧化物酶体，这与代谢改变相对应。

    关键词：FOXP3；脂质组学；溶酶体；代谢组学；ω-3长链多不饱和脂肪酸；PPAR-gamma；过氧化物酶体；RRAR-alpha；调节性T细胞；三酰基甘油。

    关键词：整合转录组学; 代谢组学; 调节性T细胞; 激活

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    期刊名：Immunobiology

    缩写：IMMUNOBIOLOGY

    ISSN：0171-2985

    e-ISSN：1878-3279

    IF/分区：2.5/Q4

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