T cell transcriptomes in simulated microgravity in vivo

Spaceflight exposes astronauts to a combination of stressors, among which microgravity remains the least well characterized at the level of human immune cell function. We examined the in vivo effect of long-term simulated microgravity (SMG) on T cell transcriptomes in ten healthy male volunteers who completed a three-week dry immersion protocol without countermeasures. Peripheral blood was collected at five time points covering a pre-immersion baseline (day -7), three intra-exposure time points (days 7, 14 and 21) and a recovery time point one week after the end of exposure (day 28). CD3+ T cells were isolated and analysed by RNA-seq, with differential expression assessed per volunteer and KEGG pathway enrichment used to identify the most affected gene networks. SMG was associated with transcript-level changes in genes mapping to key molecular pathways, including those involved in cell proliferation, cell-cycle regulation, maintenance of genome integrity, and oncogenic and tumour-suppressor networks. Hub genes shared across the most significant pathways were differentially expressed in the majority of volunteers. A notable finding was pronounced inter-individual heterogeneity: samples clustered primarily by volunteer identity, yet a coordinated temporal shift during exposure and a partial return toward baseline by day 28 were detectable across donors, and these changes occurred in the absence of detectable systemic inflammation. These results indicate that SMG is associated with altered T cell transcriptional programs in vivo and that the response is sufficiently variable between individuals to favor personalized rather than uniform countermeasure strategies.