May the Force Be with You (Or Not): The Immune System under Microgravity

ElGindi, Mei; Sapudom, Jiranuwat; Ibrahim, Ibrahim Hamed; Al-Sayegh, Mohamed; Chen, Weiqiang; Garcia-Sabaté, Anna; Teo, Jeremy C. M.

doi:10.3390/cells10081941

Cited by 39 publications

(30 citation statements)

References 158 publications

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“…It is now known that individual mammalian cells in culture are capable of responding to changes in gravitational forces. However, as recent reviews show, the form of responses is complex [ 1 , 2 , 3 , 4 , 5 ]. Cells respond to both hypergravity created by centrifugation [ 6 , 7 , 8 , 9 ] and microgravity (µG).…”

Section: Introductionmentioning

confidence: 99%

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Zhang

Thomas

Chiu

et al. 2022

IJMS

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Cultured mammalian cells have been shown to respond to microgravity (μG), but the molecular mechanism is still unknown. The study we report here is focused on molecular and cellular events that occur within a short period of time, which may be related to gravity sensing by cells. Our assumption is that the gravity-sensing mechanism is activated as soon as cells are exposed to any new gravitational environment. To study the molecular events, we exposed cells to simulated μG (SμG) for 15 min, 30 min, 1 h, 2 h, 4 h, and 8 h using a three-dimensional clinostat and made cell lysates, which were then analyzed by reverse phase protein arrays (RPPAs) using a panel of 453 different antibodies. By comparing the RPPA data from cells cultured at 1G with those of cells under SμG, we identified a total of 35 proteomic changes in the SμG samples and found that 20 of these changes took place, mostly transiently, within 30 min. In the 4 h and 8 h samples, there were only two RPPA changes, suggesting that the physiology of these cells is practically indistinguishable from that of cells cultured at 1G. Among the proteins involved in the early proteomic changes were those that regulate cell motility and cytoskeletal organization. To see whether changes in gravitational environment indeed activate cell motility, we flipped the culture dish upside down (directional change in gravity vector) and studied cell migration and actin cytoskeletal organization. We found that compared with cells grown right-side up, upside-down cells transiently lost stress fibers and rapidly developed lamellipodia, which was supported by increased activity of Ras-related C3 botulinum toxin substrate 1 (Rac1). The upside-down cells also increased their migratory activity. It is possible that these early molecular and cellular events play roles in gravity sensing by mammalian cells. Our study also indicated that these early responses are transient, suggesting that cells appear to adapt physiologically to a new gravitational environment.

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Section: Introductionmentioning

confidence: 99%

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Zhang

Thomas

Chiu

et al. 2022

IJMS

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“…However, little is known about how the lack of gravity will affect the health of space travelers. It has been shown that spaceflight and microgravity conditions can cause adverse effects on the immune system, neurological function, and bone density [ 1 , 2 , 3 ]. Several in vitro and animal studies report problems such as skin irritation and impaired wound healing under microgravity conditions [ 4 , 5 , 6 , 7 , 8 , 9 ], suggesting that this process could also be altered in astronauts during spaceflight.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model

Sapudom

ElGindi

Arnoux

et al. 2021

IJMS

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Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofibroblasts, which contribute functionally through extracellular matrix production and remodeling. In this work, we utilized collagen-based three-dimensional (3D) matrices to mimic interstitial tissue and studied fibroblast differentiation under simulated microgravity (sµG). Our results demonstrated that alpha-smooth muscle actin (αSMA) expression and translocation of Smad2/3 into the cell nucleus were reduced upon exposure to sµG compared to the 1g control, which suggests the impairment of fibroblast differentiation under sµG. Moreover, matrix remodeling and production were decreased under sµG, which is in line with the impaired fibroblast differentiation. We further investigated changes on a transcriptomic level using RNA sequencing. The results demonstrated that sµG has less effect on fibroblast transcriptomes, while sµG triggers changes in the transcriptome of myofibroblasts. Several genes and biological pathways found through transcriptome analysis have previously been reported to impair fibroblast differentiation. Overall, our data indicated that fibroblast differentiation, as well as matrix production and remodeling, are impaired in 3D culture under sµG conditions.

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“…Other notable medical events were upper respiratory symptoms such as congestion, rhinitis and sneezing (0.97/flight year), followed by various other symptoms such as cold sores, ear problems, and infectious symptoms (>0.3/flight year). This increase in skin sensitivity, reported as rashes during flight, might be a consequence of a dysregulated immune system in microgravity [ 13 , 14 , 15 ]. Furthermore, increased skin sensitivity, skin thinning and delayed wound healing, as well as increased susceptibility for skin infections, have been reported [ 16 ].…”

Section: Current Knowledge On Spaceflight-induced Skin Health Effectsmentioning

confidence: 99%

“…As such, skincare related to cleaning and moisturizing, as well as reducing injuries obtained from hardware such as spacesuits, should be optimized. Furthermore, a dysregulation of the immune system in microgravity can further contribute to the symptoms of skin sensitivity and rashes, and can delay wound healing [ 13 , 14 , 15 , 96 ]. Therefore, better understanding of immune function during long-term spaceflight, and how this may contribute to observed skin sensitivity, is desirable.…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Spaceflight Stressors and Skin Health

et al. 2022

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Traveling to space puts astronauts at risk of developing serious health problems. Of particular interest is the skin, which is vitally important in protecting the body from harmful environmental factors. Although data obtained from long-duration spaceflight studies are inconsistent, there have been indications of increased skin sensitivity and signs of dermal atrophy in astronauts. To better understand the effects of spaceflight stressors including microgravity, ionizing radiation and psychological stress on the skin, researchers have turned to in vitro and in vivo simulation models mimicking certain aspects of the spaceflight environment. In this review, we provide an overview of these simulation models and highlight studies that have improved our understanding on the effect of simulation spaceflight stressors on skin function. Data show that all aforementioned spaceflight stressors can affect skin health. Nevertheless, there remains a knowledge gap regarding how different spaceflight stressors in combination may interact and affect skin health. In future, efforts should be made to better simulate the spaceflight environment and reduce uncertainties related to long-duration spaceflight health effects.

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May the Force Be with You (Or Not): The Immune System under Microgravity

Cited by 39 publications

References 158 publications

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector

Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model

Spaceflight Stressors and Skin Health

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