Spaceflight alters expression of microRNA during T‐cell activation

Hughes‐Fulford, Millie; Chang, Tzu-Ming; Martinez, Emily; Li, Chai-Fei

doi:10.1096/fj.15-277392

Cited by 46 publications

(50 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the effects of microgravity on immune function have received increased attention and have been investigated using astronaut leukocytes, 5 space-flown mice and rats, 6,7 and in vitro cell culture. 8 Together, data from the International Space Station, Skylab, and space shuttle suggest that dysregulated immune cell-mediated cytokine secretion is a major mechanism leading to spaceflightassociated immune dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…8 Together, data from the International Space Station, Skylab, and space shuttle suggest that dysregulated immune cell-mediated cytokine secretion is a major mechanism leading to spaceflightassociated immune dysfunction. 5,[9][10][11][12] For example, after space travel, shifts occur in circulating cytokines, including increased levels of T lymphocytes producing IL-4, IL-8, IL-17, and IFN-γ 8,13,14 and decreased production of IL-1, IL-6, IL-12, and TNF-α in monocytes/ macrophages. [15][16][17][18] However, the causes of these immune cell dysfunctions and the associated changes in innate (macrophages and NK cells) and adaptive (T-cell) functions have not been extensively and systematically examined.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

et al. 2020

View full text Add to dashboard Cite

Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Although it had an unknown role, miR‐206 expression was significantly decreased in gastrocnemius from mice flown on the Space Shuttle compared with ground control samples (22). In human T cells that were stimulated with mitogens when on the International Space Station (ISS), miR‐21 was significantly up‐regulated, a change believed to play a role in the compromised immune function seen in space (23). Investigations of changes in miRNA expression by using simulated microgravity on the ground have also been reported, including one of our own studies (20, 24).…”

mentioning

confidence: 99%

Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight

et al. 2016

View full text Add to dashboard Cite

Microgravity, or an altered gravity environment different from the 1 g of the Earth, has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies that have been conducted in space or by using simulated microgravity on the ground have focused on the growth or differentiation of these cells. It has not been specifically addressed whether nonproliferating cultured cells will sense the presence of microgravity in space. In an experiment conducted onboard the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 d, respectively, to investigate changes in gene and microRNA (miRNA) expression profiles in these cells. Results of the experiment showed that on d 3, both the flown and ground cells were still proliferating slowly, as measured by the percentage of Ki-67(+) cells. Gene and miRNA expression data indicated activation of NF-κB and other growth-related pathways that involve hepatocyte growth factor and VEGF as well as the down-regulation of the Let-7 miRNA family. On d 14, when the cells were mostly nonproliferating, the gene and miRNA expression profile of the flight sample was indistinguishable from that of the ground sample. Comparison of gene and miRNA expressions in the d 3 samples, with respect to d 14, revealed that most of the changes observed on d 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeletal changes via immunohistochemistry staining of the cells with antibodies for α-tubulin and fibronectin showed no difference between the flown and ground samples. Taken together, our study suggests that in true nondividing human fibroblast cells in culture, microgravity experienced in space has little effect on gene and miRNA expression profiles.-Zhang, Y., Lu, T., Wong, M., Wang, X., Stodieck, L., Karouia, F., Story, M., Wu, H. Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight.

show abstract

“…Microgravity plays a major role in activating the self-limiting gene expression through miR-21. In microgravity the miR-21 will maturate and accumulates causing the inhibition of translation of the target genes, thus suppressing normal immune responses that would occur at ground level [10]. The heat map found in Hughes-Fulford et al study shows the expression of 17 significant gene targets of miR-21 from three donors that regulated differently after 1.5 h of activation.…”

Section: Lymphocyte Activationmentioning

confidence: 97%

Lymphocyte Signaling and Function in Altered Physiological Environments

Mann¹,

Okoro²,

Sodipe³

et al. 2019

Lymphocytes

View full text Add to dashboard Cite

The immune system is the body's defense against infectious organisms and other invaders. It is our immune system that keeps us healthy as we drift through a sea of pathogens. Healthy immune function depends on meticulous regulation of lymphocyte activation. Previous studies have shown unfavorable effects of μg on several physiological systems, including a significant reduction of the adaptive immune response. Lymphocyte movement through interstitium is critically important for the immune response. Thus, the activation of lymphocytes depends on various factors such as cell-to-cell contact due to temporary contact, permanent aggregation or by the uptake of soluble factors such as interleukin 1. Microgravity induced loss of lymphocyte locomotory activity, along with diminished lymphocyte activation, can be counteracted by nutritional supplements such as nucleotides. A study conducted by Andreazzoli et al., proposes that the knowledge of cellular and molecular mechanisms of gravity and its influence on T cells is required for creating the provision of therapeutic and possible preventive targets to keep the bone and immune systems of astronauts fully functional during long-term space missions, in addition to aiding regular people with immune deficiencies. When an immune system is compromised it can lead to various infections as well as cancerous growths. Discovering the ins and outs of the lymphocyte regulatory pathways can account for controlling and studying medicinal treatments for all forms or immune disorders. Therefore, studying both the long-term and short-term effects of microgravity is of great significance, as it has an invalidation nature that affects how the regulators of the immune system are readily able to function.

show abstract

Spaceflight alters expression of microRNA during T‐cell activation

Cited by 46 publications

References 28 publications

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight

Lymphocyte Signaling and Function in Altered Physiological Environments

Contact Info

Product

Resources

About