A good night’s sleep promotes immunity

In a recent study published in the Journal of Experimental Medicine, researchers in the United States have used mouse models to understand how sleep fragmentation affects immunological responses and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs). They also conducted a sleep restriction trial in humans to determine HPSC programming and hematopoiesis.

Study: Sleep exerts lasting effects on the function and diversity of hematopoietic stem cells. Image Credit: Yuganov Konstantin/Shutterstock


Sleep deprivation is known to impact human health on different levels. Studies have shown that sleep is necessary for the optimal functioning of the immune system, influencing the outcomes of cardiovascular disease (CVD), neurodegenerative diseases and cancer. Sleep is known to play a role in modulating the synthesis of various inflammation and immune response signaling molecules.

Research on sleep deprivation and disease in mice has shown that adequate sleep reduces HPSC cycling in the bone marrow, limiting leukocytosis. It has also been observed to reduce damage in atherosclerotic cardiovascular disease in mice and humans by lowering blood levels of monocytes and neutrophils.

Despite the plethora of evidence linking sleep to various disease outcomes and overall health, chronic sleep disruption is a prevalent problem of the modern era. Recent findings that suggest that catch-up sleep does not compensate for disrupted sleep further underscore the role of sleep in human health. However, the cellular and epigenetic mechanisms by which lack of sleep affects the immune system remain unexplored.

About the study

In the present study, researchers quantified sleep and wake states and transition periods by measuring electroencephalography (EEG) and electromyography (EMG) signals from the brain and muscle, respectively, in models of mice subjected to sleep fragmentation.

The epigenome of hematopoietic progenitor cells has been profiled to understand stem-intrinsic mechanisms of how sleep mediates hematopoiesis. This included measuring histone deacetylase (HDAC) activity in hematopoietic progenitor cells from dormant fragmented mice. Additionally, transposase-accessible chromatin sequencing (ATAC-seq) assays were performed on mice that received habitual sleep, fragmented sleep, and fragmented sleep, followed by recovery sleep.

Circulating leukocytes were analyzed by flow cytometry. The enzyme immunoassay (ELISA) was used to measure the levels of granulocyte colony stimulating factor (G-CSF), macrophage colony stimulating factor (M-CSF), tumor necrosis factor alpha ( TNFα), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β).


The results indicated that sleep fragmentation intensifies sleep-wake transitions, consequently increasing hematopoiesis and causing histone acetylation that alters the epigenome of HSPCs in mice. During recovery from sleep, although hematopoiesis decreased, the epigenetic imprint of HSPCs remained, causing heightened inflammatory responses to subsequent immune challenges.

Using a multicolor fluorescent tracking system, the researchers found that hematopoietic clonal diversity decreased with interrupted sleep. Sleep restriction trials in humans have shown an increase in monocytes and HSPCs in the blood and a reduction in histone HSPC acetylation. The authors believe that fragmented sleep increased myeloid HSPC signals. ELISA results also showed that the sleep-mediated increase in HPSC is controlled by hypothalamic hypocretinergic signals, with fragmented sleep resulting in elevated IL-6 levels.

Previous research has shown that sleep disorders such as insomnia and obstructive sleep apnea (OSA) cause epigenetic changes in circulating leukocytes, cardiovascular system, altered deoxyribonucleic acid (DNA) methylation in liver and muscle tissue and caused rapid epigenetic aging of blood leukocytes. . The results of this study provided evidence that these epigenetic changes are partially maintained and impact future immune function and disease pathology.

The mouse model-based study indicated that even when followed by 10 weeks of recovery sleep, 16 weeks of sleep fragmentation results in elevated levels of monocytes, hematopoietic stem cells containing LinSc1+c-Kit+ (LSK) and plasma IL-6 and TNFα. These changes were also found to be intrinsic to hematopoietic cells, with bone marrow transfer experiments causing aggressive inflammatory responses and increased monocyte production and bone marrow hematopoiesis.


Taken together, the study results suggest that fluctuations in sleep quality and duration cause sustained epigenetic changes in HSPCs and reduce clonal hematopoietic diversity, leading to exaggerated inflammatory responses to subsequent infections. The authors believe the findings highlighted the importance of good sleep habits early in life, which could reduce future disease severity, particularly for inflammatory diseases such as cardiovascular disease and cancer.

While previous studies have identified genetic mutations that result in hematopoietic stem cell proliferation, the present study demonstrated that sleep deprivation-induced stress on the hematopoietic system leads to similar hematopoietic stem cell proliferation and exaggerated immune responses. later without the presence of driver mutations.

Sleep deprivation is a chronic problem, especially in young adults. The study highlights the importance of establishing healthy sleep habits early in life to maintain a normally functioning immune system.

Journal reference:

  • McAlpine, CS, Kiss, MG, Zuraikat, FM, Cheek, D., Schiroli, G., Amatullah, H., Huynh, P., Bhatti, MZ, Wong, L.-P., Yates, AG, Poller, WC, Mindur, JE, Chan, CT, Janssen, H., Downey, J., Singh, S., Sadreyev, RI, Nahrendorf, M., Jeffrey, KL and Scadden, DT (2022). Sleep exerts lasting effects on the function and diversity of hematopoietic stem cells. Journal of Experimental Medicine, 219(11). https://doi.org/10.1084/jem.20220081, https://rupress.org/jem/article/219/11/e20220081/213487/Sleep-exerts-lasting-effects-on-hematopoetic-stem

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