Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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T Cell Activation in Microgravity Compared to 1g (Earth's) Gravity

ABSTRACT: This study tested the hypothesis that transcription of immediate early genes is inhibited in T cells activated in microgravity (mg). Immunosuppression during spaceflight is a major barrier to safe long-term human space habitation and travel. The goals of these experiments were to prove that mg was the cause of impaired T cell activation during spaceflight as well as understand the mechanisms controlling early T cell activation. T cells from 4 human donors were stimulated with concanavalin A (ConA) and anti-CD28 onboard the International Space Station (ISS). An onboard centrifuge was used to generate a 1g simultaneous control to isolate the effects of mg from other variables of spaceflight. Microarray expression analysis after 1.5 hours of activation demonstrated that mg- and 1g-activated T cells had distinct patterns of global gene expression and identified 47 genes that were significantly differentially down-regulated in mg. Importantly, several key immediate early genes were inhibited in mg. T cells were isolated from human volunteers. T cells from each donor were kept separate and loaded into individual chambers in separate cassettes for the following treatments: mg non-activated, mg activated, and 1g activated. Therefore, samples represent biological triplicates. Experimental units were launched into space and placed into the KUBIK facility onboard the International Space Station. The 1g units were placed in the central centrifuge positions and centrifuged with an applied 1g force. The mg units were place in the static positions for continued mg exposure. After 30 minutes of pre-incubation, mg non-activated units were fixed by addition of RNALater (QIAGEN, Valencia, CA), removed from the incubator, and stored in 4M-BM-0C. The mg and 1g activated units were injected with final concentration 10mg/ml Con A and 4mg/ml anti-CD28. These cassettes were replaced into KUBIK on either the centrifuge or static positions and activated for 1.5 hours. Activation was stopped with the addition of RNALater and the units were then moved to 4M-BM-0C storage. All units were returned to Earth for analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Tammy Chang

PROVIDER: E-GEOD-38836 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Genome-wide transcriptional profiling shows that reducing gravity levels in the International Space Station (ISS) causes important alterations in Drosophila gene expression. However, simulation experiments on ground, without space constraints, show weaker effects than space environment. A global and integrative analysis using the M-bM-^@M-^\gene expression dynamics inspectorM-bM-^@M-^] (GEDI) self-organizing maps, reveals a subtle response of the transcriptome using different populations and microgravity and hypergravity simulation devices. These results suggest that, in addition to behavioural responses that can be detected also at the gene expression level, the transcriptome is finely tuned to normal gravity. The alteration of this constant parameter on Earth can have effects on gene expression that depends both on the environmental conditions and the ground based facility used to compensate the gravity vector. Alternative and commons effects of mechanical facilities, like the Random Positioning Machine and a centrifuge, and strong magnetic field ones, like a cryogenically cooled superconductive magnet, are discussed. We compare the effects over the gene expression profile of different gender/age Drosophila imagoes in 3-4 days-long experiments under altered gravity conditions into three GBF ("Ground Based Facilities" for micro/hyper- gravity simulation) using whole genome microarray platforms. Descriptions of different GBFs ("treatments"): LDC means "Large Diameter Centrifuge". Samples can be placed under three conditions: inside LDC (at certain g level), at the LDC rotational control and at external 1g control (outside the LDC). RPM means "Random Positioning Machine". Samples can be placed under two conditions: inside RPM (at nearly 0g, Microgravity level) and at external 1g control (outside the RPM). At the magnet, means INSIDE the Magnetic levitator (another GBF). Samples can be placed under four conditions: inside Magnet 0g* (at microgravity with magnetic field), inside Magnet at 1g* (internal control with magnetic field) or inside the magnet 2g* (at hypergravity with magnetic field) and at external 1g control (outside the magnet)

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T Cell Activation in Microgravity Compared to 1g (Earth's) Gravity

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