Space Radiation and Microgravity Effects on Immune Transcriptomes: A Systematic Review and Meta-Analysis
Year: 2026
Type: study-registration
Abstract: Purpose. Astronauts on long missions are exposed to space radiation and microgravity at the same time, but most ground-based studies of immune cells test these stressors one at a time. It is not known whether their combined effect on immune gene expression is additive, greater than additive or smaller than additive. Individual transcriptomic studies are small and use different cell types, platforms and analysis pipelines, so a quantitative synthesis is needed. Design. This is a systematic review and meta-analysis of transcriptome-wide studies (microarray, bulk or single-cell RNA sequencing, genome-wide DNA methylation) of human and mouse immune cells and lymphoid tissues exposed to space-relevant ionising radiation, real or simulated microgravity, spaceflight, or radiation combined with microgravity, compared with an unexposed or pre-exposure control. PubMed, Scopus and Europe PMC were searched, together with the NASA Open Science Data Repository, Gene Expression Omnibus and ArrayExpress. The review follows the PRISMA 2020 statement. Research questions. (1) Is there a common transcriptional signature of space stressors in immune cells, and how do the signatures of radiation, microgravity and spaceflight differ? (2) Do radiation and microgravity interact when applied together in factorial studies? (3) Are spaceflight-induced changes in immune transcriptomes transient or persistent after return to Earth? Methods. Data are extracted at the level of the contrast (one exposed group versus one control group). Where raw or count-level data are available, they are reprocessed with a uniform pipeline (linear models with empirical Bayes moderation). Gene-level log2 fold changes are pooled by random-effects meta-analysis within each stressor group, with one contrast per independent cohort. Gene-set responses are tested with correlation-adjusted competitive tests (CAMERA) on MSigDB Hallmark gene sets. In complete two-by-two factorial studies, the radiation × microgravity interaction is tested at the gene-set level. Persistence is assessed in astronaut time series. Risk of bias is assessed with seven domains adapted from the SYRCLE tool. Sensitivity analyses include human-only data, secondary contrasts, leave-one-out analyses, subgroups, and an alternative random-effects model (Hartung–Knapp–Sidik–Jonkman). Expected outcomes. A characterisation of reproducible and stressor-specific transcriptional responses of immune cells to space stressors; an estimate of whether radiation and microgravity interact; an assessment of post-flight persistence; and an evaluation of the evidence gaps, in particular the number and quality of factorial studies. Retrospective registration. This review is registered retrospectively. Searching, screening, data extraction and analysis were completed on 13 October 2026, before this registration. The methods described here are those that were used; deviations from the original plan are listed under Context and additional information.
Source: Open Science Framework
Author: TALYA MORGUL
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221636681