Multi-omics profiling reveals immune suppression and antigen presentation deficits following human spaceflight
Year: 2025
Type: article
Abstract: Human spaceflight imposes unique physiological stressors that disrupt immune homeostasis, yet the molecular mechanisms underlying postflight immune dysfunction remain poorly understood. Here, we present an integrative, multi-omic secondary analysis of peripheral blood mononuclear cells (PBMCs) from the Inspiration4 mission [28] using publicly available data from NASA’s Open Scenc Data Repository (OSDR), integrating single-nucleus RNA sequencing (snRNA-seq), single-nucleus ATAC sequencing (snATAC-seq), and plasma proteomics. We identify broad transcriptional suppression of key antigen presentation genes—including HLA-A, HLA-B, HLA-C, and CD74—across multiple immune cell types postflight, with HLA-C showing the strongest reduction (log₂FC = –1.7, p < 0.01) in CD16⁺ monocytes. Concordant chromatin accessibility changes were observed in genes such as PDK4, CD86, and NR3C1, indicating epigenetic regulation of metabolic and immunomodulatory programs. Integration of matched snRNA-seq and snATAC-seq data revealed gene-specific coherence in transcriptional and epigenetic responses, particularly in monocytes. Proteomic validation using serum cytokine measurements from the NASA LSDS-8 Alamar panel confirmed statistically significant declines in circulating TGFB1 and CXCL2 (2.8% and 2.3% respectively, p < 0.05), aligning with transcriptional trends. Functional enrichment analysis highlighted postflight repression of interferon signaling, antigen processing, and glucocorticoid-responsive pathways. Given the small sample size (n=4), these findings should be considered preliminary but provide important proof-of-concept evidence for multi-layered immune suppression following spaceflight. Together, these findings delineate a multi-layered signature of immune suppression following spaceflight and establish a framework for cell-type–resolved, cross-platform immunomonitoring in future human missions.
Author: Zhao, Linda Dianling
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7104620982
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