CLEC1B and RAC1 in peripheral immune remodeling associated with sleep disturbance: an exploratory integrative study

Sleep disturbance is closely linked to immune dysfunction, but the molecular features of associated peripheral immune remodeling remain incompletely defined.

In this exploratory study, we integrated blood eQTL data and GWAS summary statistics with mouse PBMC single-cell data, a human PBMC transcriptome cohort, and mouse PBMC measurements. The single-cell dataset comprised one control, one 24-hour sleep-deprivation, and one 48-hour sleep-deprivation library. Descriptive single-cell patterns showed contraction of the B-cell compartment and expansion of granulocytes. Mendelian randomization nominally prioritized RAC1 and CLEC1B, with limited co-localization support. Both genes showed lower expression in the human cohort and were associated with altered B-cell communication and metabolic states. In mouse PBMCs (n = 3 per group), Clec1b qPCR showed a downward trend (P = 0.072), whereas Rac1 qPCR expression was lower after sleep deprivation (P = 0.017). Lane-level western blot analysis also showed lower CLEC1B (P = 0.0056) and RAC1 (P = 0.0016) protein abundance.

These exploratory integrative analyses nominate CLEC1B and RAC1 as candidate genes associated with peripheral B-cell remodeling in a sleep-disturbance context. These hypothesis-generating findings warrant targeted functional studies of their roles in sleep-related immune remodeling.