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首页> 外文期刊>Nature >Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells
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Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells

机译：淋巴管内皮细胞S1P促进线粒体功能并在幼稚T细胞中存活

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摘要

Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide(1). Because the production of T cells declines with age, naive T cells must be long-lived(2). However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P(1) receptor (S1P(1)R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph(3). Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P(1)R on T cells, and that the requirement for S1P(1)R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival(4).
机译：有效的适应性免疫反应需要大量的天然T细胞在整个人体中迁移，从而迅速鉴定出几乎所有的外源肽（1）。由于T细胞的产生随着年龄的增长而下降，因此幼稚的T细胞必须是长寿的（2）。然而，尚不清楚幼稚的T细胞如何在持续旅行的同时存活数年。化学吸引力1-磷酸鞘氨醇（S1P）指导T细胞在次级淋巴器官（包括脾脏，淋巴结和Peyer斑块）之间的循环，T细胞在其中搜寻抗原。循环液中S1P的浓度高于淋巴器官，S1P（1）受体（S1P（1）R）指导T细胞从脾脏进入血液，从淋巴结和Peyer斑块进入淋巴（ 3）。在这里，我们显示S1P不仅对于幼稚T细胞的循环至关重要，而且对于它们的存活也至关重要。使用转基因小鼠模型，我们证明淋巴管内皮细胞通过转运蛋白SPNS2分泌S1P支持T细胞的生存，该S1P通过T1细胞上的S1P（1）R发出信号，并且对S1P（1）R的要求是不依赖于受体在引导淋巴结出口中已确立的作用。 S1P信号传导维持幼稚T细胞的线粒体含量，为细胞提供能量以继续其恒定迁移。 S1P信号通路在治疗上被靶向抑制自身反应性T细胞的运输，这些发现表明，同时靶向自身反应性或恶性细胞存活可能是可能的（4）。

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  • 来源
    《Nature》 |2017年第7656期|158-161|共4页
  • 作者

    Mendoza Alejandra; Fang Victoria; Chen Cynthia; Serasinghe Madhavika; Verma Akanksha; Muller James; Chaluvadi V. Sai; Dustin Michael L.; Hla Timothy; Elemento Olivier; Chipuk Jerry E.; Schwab Susan R.;

  • 作者单位

    NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA;

    NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA;

    NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA;

    Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA;

    Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10021 USA;

    NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA;

    NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA;

    NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA|Univ Oxford, Kennedy Inst Rheumatol, Roosevelt Dr, Oxford OX3 7FY, England;

    Harvard Med Sch, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA;

    Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10021 USA;

    Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA;

    NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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