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太空飞行和模拟微重力会导致早期T细胞活化过程中关键基因表达显著降低。

Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.

作者信息

Martinez Emily M, Yoshida Miya C, Candelario Tara Lynne T, Hughes-Fulford Millie

机构信息

Hughes-Fulford Laboratory, Department of Medicine Metabolism Division San Francisco Department of Veterans Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, California; and.

Hughes-Fulford Laboratory, Department of Medicine Metabolism Division San Francisco Department of Veterans Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, California; and Department of Medicine, University of California, San Francisco, California

出版信息

Am J Physiol Regul Integr Comp Physiol. 2015 Mar 15;308(6):R480-8. doi: 10.1152/ajpregu.00449.2014. Epub 2015 Jan 7.

Abstract

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.

摘要

健康的免疫功能依赖于淋巴细胞激活的精确调控。在美国国家航空航天局(NASA)的阿波罗和航天飞机时代,多项太空飞行研究表明,在微重力(μg)条件下淋巴细胞活性会降低。地面科学家使用两种模拟微重力(sμg)模型:1)旋转壁式生物反应器(RWV)和2)随机定位机(RPM),以便在国际空间站(ISS)有太空飞行机会从而开展真正的微重力研究之前,研究重力改变对细胞功能的影响。本研究的目的是比较真正的微重力和模拟微重力对来自太空飞行动物和地面动物的小鼠脾细胞中关键早期T细胞激活基因表达的影响。我们首次在Il2、Il2rα、Ifnγ和Tagap的免疫基因激活过程中比较了微重力太空飞行、RPM和RWV这三种条件;此外,我们证实了两个新的早期T细胞激活基因Iigp1和Slamf1。使用定量实时PCR(qRT-PCR)分析所有样本的基因表达。我们的结果表明,在太空飞行、RPM和RWV样本中,小鼠免疫功能受到抑制,而激活的地面样本中的基因表达显著增加。这些发现表明,模拟微重力模型为科学家开展基线研究和在太空飞行实验中增强真正的微重力提供了一个绝佳的试验平台。最终,淋巴细胞的模拟微重力和太空飞行研究可能会为新的调控途径提供见解,这将造福未来的宇航员以及地球上患有免疫疾病的人们。

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