Department of Biology, Faculty of Science, University of Ottawa, Ottawa, ON, Canada.
Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Front Immunol. 2023 Jun 22;14:1171103. doi: 10.3389/fimmu.2023.1171103. eCollection 2023.
Spaceflight leads to the deconditioning of multiple body systems including the immune system. We sought to characterize the molecular response involved by capturing changes in leukocyte transcriptomes from astronauts transitioning to and from long-duration spaceflight.
Fourteen male and female astronauts with ~6-month- long missions aboard the International Space Station (ISS) had 10 blood samples collected throughout the three phases of the study: one pre-flight (PF), four in-flight (IF) while onboard the ISS, and five upon return to Earth (R). We measured gene expression through RNA sequencing of leukocytes and applied generalized linear modeling to assess differential expression across all 10 time points followed by the analysis of selected time points and functional enrichment of changing genes to identify shifts in biological processes.
Our temporal analysis identified 276 differentially expressed transcripts grouped into two clusters (C) showing opposite profiles of expression with transitions to and from spaceflight: (C1) decrease-then-increase and (C2) increase-then-decrease. Both clusters converged toward average expression between ~2 and ~6 months in space. Further analysis of spaceflight transitions identified the decrease-then-increase pattern with most changes: 112 downregulated genes between PF and early spaceflight and 135 upregulated genes between late IF and R. Interestingly, 100 genes were both downregulated when reaching space and upregulated when landing on Earth. Functional enrichment at the transition to space related to immune suppression increased cell housekeeping functions and reduced cell proliferation. In contrast, egress to Earth is related to immune reactivation.
The leukocytes' transcriptome changes describe rapid adaptations in response to entering space followed by opposite changes upon returning to Earth. These results shed light on immune modulation in space and highlight the major adaptive changes in cellular activity engaged to adapt to extreme environments.
太空飞行会导致包括免疫系统在内的多个身体系统的功能失调。我们试图通过捕获从前往和返回长期太空飞行的宇航员的白细胞转录组中的变化来描述所涉及的分子反应。
14 名男性和女性宇航员在国际空间站（ISS）上进行了约 6 个月的任务，在研究的三个阶段共采集了 10 个血液样本：一个飞行前（PF）、四个在ISS 上的飞行中（IF）和五个返回地球（R）时。我们通过白细胞的 RNA 测序测量基因表达，并应用广义线性模型评估所有 10 个时间点的差异表达，然后分析选定的时间点和变化基因的功能富集，以确定生物过程的变化。
我们的时间分析确定了 276 个差异表达的转录本，分为两个簇（C），它们的表达模式随着往返太空而相反：（C1）先下降后上升，（C2）先上升后下降。两组都在太空中约 2 到 6 个月之间收敛到平均表达水平。对太空飞行过渡的进一步分析确定了下降-然后增加的模式，PF 和早期太空飞行之间有 112 个下调基因，晚期 IF 和 R 之间有 135 个上调基因。有趣的是，有 100 个基因在到达太空时同时下调，在降落在地球时又上调。过渡到太空时与免疫抑制相关的功能富集增加了细胞管家功能，减少了细胞增殖。相反，向地球的出口与免疫再激活有关。
白细胞转录组的变化描述了对进入太空的快速适应，然后在返回地球时发生相反的变化。这些结果揭示了太空环境下的免疫调节，并强调了为适应极端环境而进行的细胞活动的主要适应性变化。
