Objectives: 

Several experiments performed during spaceflight clearly show that microgravity (μg) affect important cellular mechanisms like proliferation, differentiation, genetic expression, cytoskeleton architecture and motility in lymphocytes, monocytes and in other mammalian cells. In particular, a dramatic depression of the mitogenic in vitro activation of human T lymphocytes was observed in low gravity. In fact, immunosuppression during spaceflight is a major barrier to safe long-term human space habitation and travel. The aim of LEUKIN experiment was to identify the immediate early genes whose transcription may be inhibited in μg and understand the mechanisms controlling early T cell activation.

Materials: 

Human T cells were stimulated with T cell mitogen concanavalin A and anti-CD28 on board the International Space Station (ISS). Importantly, an onboard centrifuge was used to generate a 1xg simultaneous control to isolate the effects of μg from other variables of spaceflight. The gene expression was evaluated by cDNA microarray and qRT-PCR techniques.

Results: 

Microarray expression analysis after 1.5 hours of activation demonstrated that μg and 1xg-activated T cells had distinct patterns of global gene expression and identified 47 genes that were significantly differentially down-regulated by at least 2 fold in μg. Expression of many genes involved in mitogenesis, cytokine production, apoptosis, and signal transduction and several key immediate early genes were inhibited in μg.

Conclusions: 

Our results suggest that the TNF pathway and downstream effectors functions likely will be severely impaired in immune responses in μg and that transactivation of Rel/NFκB, CREB, and SRF gene targets were down-regulated. Expression of cREL gene targets were significantly inhibited and transcription of cREL itself was significantly reduced in μg. Future research should focus on delineating the specific mechanisms of how μg causes dysregulation of these signal transduction pathways in order to further clarify the molecular basis of immunosuppression during spaceflight.