DS modulates B-cell-related immune signaling, with reduced TLR7 and increased BANK1 expression in a sex- and mood-dependent manner.
Key Findings
Results
Acute sleep deprivation reduced TLR7 mRNA expression across all subgroups examined.
TLR7 expression was reduced in the entire study group following sleep deprivation (p < 0.001).
The reduction was observed within Responders, Non-Responders, and both male and female subgroups (all p < 0.001).
76 adults underwent polysomnography (PSG) followed by sleep deprivation.
Gene mRNA expression was measured in peripheral blood mononuclear cells using qRT-PCR.
Blood was collected after PSG (baseline) and again after sleep deprivation.
Results
Women exhibited higher TLR7 expression than men following sleep deprivation, independent of age and BMI.
The sex difference in post-deprivation TLR7 expression was statistically significant (p = 0.022).
This difference was identified during analysis of covariance (ANCOVA), controlling for age and body mass index (BMI).
The finding suggests a sex-specific modulation of TLR7 signaling in response to acute sleep loss.
Results
Women showed lower baseline TLR9 expression than men, a difference that was abolished after sleep deprivation.
At baseline (post-PSG), women exhibited lower TLR9 expression than men (p = 0.009), independent of age and BMI.
After sleep deprivation, the sex difference in TLR9 expression was no longer statistically significant (p = 0.570).
This suggests sleep deprivation selectively altered TLR9 expression in a sex-dependent manner, equalizing expression between sexes.
Results
BANK1 mRNA expression increased following sleep deprivation in the entire study group and in Non-Responders, but not in Responders.
BANK1 expression increased post-sleep deprivation in the entire study group (p = 0.021).
The increase was significant in Non-Responders (NRs) (p = 0.021) but not in Responders (REs) (p = 0.329).
Participants were classified as Responders or Non-Responders based on mood changes after sleep deprivation, assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).
This indicates that emotional or mood response to sleep deprivation modulates the BANK1 immune signaling pathway.
Methods
Mood was evaluated before and after each experimental stage using the Montgomery-Åsberg Depression Rating Scale to classify participants by emotional response to sleep deprivation.
Participants were classified as Responders (REs) or Non-Responders (NRs) based on mood changes post-sleep deprivation.
MADRS assessments were conducted before and after both the PSG night and the sleep deprivation stage.
This classification allowed stratified analysis of immune gene expression by emotional response phenotype.
Background
Sleep deprivation is linked to increased risk of immune-mediated diseases, and TLR7, TLR9, and BANK1 are key B-cell signaling components potentially contributing to their pathogenesis.
TLR7 and TLR9 are Toll-like receptors involved in innate immune signaling.
BANK1 is a B-cell scaffold protein implicated in autoimmune disease pathogenesis.
The study was designed to investigate whether acute sleep deprivation modulates these autoimmune-relevant signaling pathways.
What This Means
This research suggests that a single night of sleep deprivation changes the activity of certain immune genes in white blood cells, specifically genes involved in how B cells (a type of immune cell) respond to threats and regulate inflammation. The study found that a gene called TLR7 was consistently reduced after sleep deprivation in all groups tested — men, women, and regardless of mood response. However, a second gene, BANK1, increased after sleep deprivation only in people whose mood did not worsen in response to the lost sleep, suggesting that emotional resilience to sleep loss may be linked to different immune responses.
The study also found notable sex differences. Women had lower levels of TLR9 gene activity than men under normal rested conditions, but this difference disappeared after sleep deprivation, meaning the immune systems of men and women responded differently to the same sleep loss. Women also maintained higher TLR7 activity than men after sleep deprivation. These findings are relevant because TLR7, TLR9, and BANK1 are all connected to autoimmune diseases such as lupus, which disproportionately affects women.
This research suggests that sleep loss does not just make people feel tired — it actively alters immune signaling pathways in ways that differ by sex and emotional response. This may help explain why chronic sleep disruption is associated with higher rates of autoimmune and inflammatory diseases, and why men and women might experience different immune consequences from sleep loss.
Ditmer M, Gabryelska A, Tarasiuk-Zawadzka A, Binienda A, Turkiewicz S, Karuga F, et al.. (2026). Acute Sleep Deprivation and the Autoimmune TLR-BANK1 Pathway: Interplay with Gender and Emotional State.. International journal of molecular sciences. https://doi.org/10.3390/ijms27010375