Sleep profoundly influences immune and inflammatory responses, protecting against age-associated immune disorders including cardiovascular disease (CVD), cancer, and neurodegenerative diseases . Despite these associations, more than half of adults do not get sufficient sleep. Sleep impacts many facets of the immune system including adaptive responses, inflammation, and the synthesis of cytokines and immune mediators.
Yet, the influence of sleep on hematopoietic stem and progenitor cells (HSPCs) and immune cell production is poorly understood. In humans, poor quality sleep and sleep disorders are associated with increased blood myeloid cells, and in murine models, sufficient sleep restricts leukocytosis by limiting HSPC cycling in the bone marrow (BM) through neuroimmune mechanisms.
In human and murine atherosclerotic CVD, prolonged sufficient sleep reduces the number of blood monocytes and neutrophils, constraining leukocyte infiltration into the arterial wall and reducing lesion size. It has remained unclear, however, how sleep might influence HSPC programming and function.
Sleep abundance and quality vary over an individual’s lifespan, and the impact of sleep variability on long-term immune-related outcomes is unclear.
Chronic, insufficient sleep can negatively affect immune cells, which may lead to inflammatory disorders and cardiovascular disease, according to a new study from the Icahn School of Medicine at Mount Sinai.
A team of investigators analyzed 14 healthy adults who regularly sleep eight hours a night. First, researchers monitored them sleeping at least eight hours a night for six weeks.
They drew their blood and analyzed their immune cells. Then, the same group of adults reduced their sleep time by 90 minutes every night for six weeks, and had their blood and immune cells reanalyzed. At the end of the study researchers compared the blood and cell samples from the full night’s sleep and restricted sleep periods.
All participants had significant changes in their immune cells (also known as hematopoietic cells) due to a lack of sleep — there were more of them, and the DNA structure was altered. After six weeks of sleep restriction, they had an increased number of immune cells.
Researchers also analyzed sleep in mouse models. Groups of mice were either allowed to sleep undisturbed, or had sleep fragmentation, where they were awakened throughout the night for 16 weeks.
Then, mice with sleep fragmentation went through uninterrupted sleep recovery for ten weeks. Investigators took immune stem cells and immune cells from mice during these undisturbed, fragmented, and sleep recovery phases, analyzed them and compared them at the end of the experiment.
Results in mice were consistent with results in humans. They showed that all mice with fragmented sleep had significant changes to their immune stem cells, producing an increased number of immune cells, and also showed evidence of rewiring and reprogramming. A notable finding from the mouse group was that even after sleep recovery, the immune stem cells retained this rewiring structure, and they continued to produce additional white blood cells, making the mice susceptible to inflammation and disease.
These findings suggest that sleep recovery is not able to fully reverse the effects of poor-quality sleep. We can detect a molecular imprint of insufficient sleep in immune stem cells, even after weeks of recovery sleep. This reduction in overall diversity and aging of the immune stem cell population is an important contributor to inflammatory diseases and cardiovascular disease.
Cameron S. McAlpine, Máté G. Kiss, Faris M. Zuraikat, David Cheek, Giulia Schiroli, Hajera Amatullah, Pacific Huynh, Mehreen Z. Bhatti, Lai-Ping Wong, Abi G. Yates, Wolfram C. Poller, John E. Mindur, Christopher T. Chan, Henrike Janssen, Jeffrey Downey, Sumnima Singh, Ruslan I. Sadreyev, Matthias Nahrendorf, Kate L. Jeffrey, David T. Scadden, Kamila Naxerova, Marie-Pierre St-Onge, Filip K. Swirski. Sleep exerts lasting effects on hematopoietic stem cell function and diversity. Journal of Experimental Medicine. Retrieved from : https://rupress.org/jem/article/219/11/e20220081/213487/Sleep-exerts-lasting-effects-on-hematopoietic-stem