We take a multidisciplinary approach to investigate the immune system in sleep, cardiovascular disease, and neurodegenerative diseases.
Project 1. Investigating the relationship between sleep and the brain-heart axis
The brain and heart are vital co-dependent organs and hubs of the nervous and circulatory systems respectively. Communication between these organs is critical to health and occurs through neuronal innervation and vascular supply of immune cells and molecules. The heart-brain axis is calibrated by many factors and one of the most important is sleep. Humans should spend a third of their lives asleep, yet we are becoming increasingly sleep-insufficient. Sleep is essential for proper brain and heart function. We study bidirectional integrations between sleep and the heart-brain axis.
Myocardial infarction augments sleep to limit cardiac inflammation and damage. Huynh P., Hoffmann J., Gerhardt T., Kiss M., Zuraikat F., Cohen O., Wolfram C., Yates A., Leunig A., Heiser M., Gaebel L., GianeselliM., Goswami S., Khamhoung A., Downey J., Yoon S., Chen Z., Roudko V., Dawson T., Ferreira da Silva J., Ameral N., Morgenroth-Rebin J., D’Souza D., Koekkoek L., Jacob W., Munitz J., Lee D., Fullard J., van Leent M., Roussos P., Kim-Schulze S., Shah N., Kleinstiver B., Swirski F., Leistner D., St-Onge M-P., McAlpine C. Nature. 2024
Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis. Cell. 2021 Mar 4;184(5):1348-1361.e22.
Sleep modulates haematopoiesis and protects against atherosclerosis. Nature. 2019 Feb;566(7744):383-387. doi: 10.1038/s41586-019-0948-2. Epub 2019 Feb 13.
Sleep exerts lasting effects on hematopoietic stem cell function and diversity. McAlpine C, Kiss M, Zuraikat F, Cheek D, Schiroli G, Amatullah H, Huynh P, Bhatti M, Wong LP, Yates A, Poller W, Mindur J, Chan C, Janssen H, Downey J, Singh S, Sadreyev R, Nahrendorf M, Jeffrey K, Scadden D, Naxerova K, St-Onge MP†, Swirski FK Journal of Experimental Medicine, 2022, 219(11)1-16
Project 2. How do immune cells and their products coordinate communication between the CNS and periphery in neurodegenerative disorders?
The immune system plays an important role in the pathophysiology of neurodegenerative diseases including Alzheimer’s disease (AD) and multiple sclerosis (MS). We pursue research exploring glial cell communication and the role of growth factors in mediating the biology of astrocytes, microglia, and the peripheral immune system in neurodegeneration. Interleukin-3 is a multifunctional cytokine and growth implicated in many inflammatory and autoimmune diseases. We have shown, in humans and mice, that astrocyte-sourced interleukin-3 (IL-3) programs IL-3RA-expressing microglia and other myeloid cells to generate immune recruitment and chemotactic programming. In the context of Alzheimer’s disease (AD) this is beneficent as IL-3 endows with an acute immune response program, enhanced motility, and the capacity to cluster and clear aggregates of Aβ and tau, ameliorating AD (McAlpine et al. Nature 2021). In multiple sclerosis (MS) IL-3 stimulation of myeloid chemoattraction is detrimental and perpetuates neuroinflammation and the recruitment of immune cells to the CNS to worsen MS and it’s preclinical model EAE (Kiss et al. Immunity 2023). These data highlight the importance of balancing and fine-tuning inflammation in neurodegenerative diseases and position IL-3 as a critical player in neuroinflammatory balance that could be targeted to equilibrate immune responses in the brain.
