Integrated Analysis of Immune-Related Genes Reveals Altered Biological Functions and Immune Cell Abundance in Sleep Deprivation

Introduction: Sleep deprivation is a common phenomenon in modern society and has received widespread attention. However, data about its impact on immune system functions remains scant. Methods: Three sleep deprivation-related gene datasets, GSE98564, GSE98565, and GSE98566, were downloaded from the Gene Expression Omnibus database. A total of 23 control samples and 30 sleep deprivation samples were obtained after sample processing. Differentially Expressed Genes (DEGs) and Differentially Expressed Immune-Related Genes (DEIRGs) were analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Additionally, CIBERSORT analysis, weighted gene co-expression network analysis, and consensus clustering were performed. Finally, qPCR was conducted to verify the expression of six hub immune genes in the auditory cortex, hippocampus, and hypothalamus tissues from control and sleep- -deprived mice. Results: The identified DEGs and DEIRGs affected immune and hematopoietic functions. The composition of neutrophils was significantly lower in the sleep deprivation samples than in the control group. Moreover, 32 key immune genes and five hub immune genes (HLA-DRB5, CTSE, ADIPOR1, HDGF, and ABCC4) associated with sleep deprivation were screened, which were also found to be significantly correlated with the proportions of major immune cells (naïve B cells, plasma cells, and neutrophils). Two molecular subtypes of sleep deprivation were identified, each with distinct immune genes, functions, pathways, and major immune cell composition. Discussion: Overall, the findings support the notion that sleep deprivation disrupts immune and hematopoietic pathways and alters immune-cell composition (notably reduced neutrophils with increased B-cell subsets), with hub immune genes and molecular subtypes suggesting biological heterogeneity that may inform future mechanistic and therapeutic studies. Furthermore, the function of these five hub immune genes should be investigated in both in vitro and in vivo models. Conclusions: The data from the study demonstrated that sleep deprivation affected the immune function and immune cell composition, especially neutrophil-mediated immune responses. The study reveals the underlying mechanisms of sleep deprivation-related immune disorders and offers potential treatment targets.