Claudio Vinegoni, Ph.D. | Chronic variable stress activates hematopoietic stem cells

Nat. Med.
Chronic variable stress activates hematopoietic stem cells

Heidt, T., Sager, H. B., Courties, G., Dutta, P., Iwamoto, Y., Zaltsman, A., Muhlen, C., Bode, C., Fricchione, G. L., Denninger, J., Lin, C. P., Vinegoni, C., Libby, P., Swirski, F. K., Weissleder, R., and Nahrendorf^#, M.

Nature Medicine 2014

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Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis(1,2). Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex(3,4). It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the beta(3)-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe(-/-) mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.
@article{2014-NM, author= {Heidt, T. and Sager, H. B. and Courties, G. and Dutta, P. and Iwamoto, Y. and Zaltsman, A. and von zur Muhlen, C. and Bode, C. and Fricchione, G. L. and Denninger, J. and Lin, C. P. and Vinegoni, C. and Libby, P. and Swirski, F. K. and Weissleder, R. and Nahrendorf<sup>#</sup>, M.}, title= {Chronic variable stress activates hematopoietic stem cells}, journal= {Nature Medicine}, alternatejournal = {Nat. Med.}, year = {2014}, volume = {20}, number = {7}, pages = {754-758}, issn = {1078-8956}, doi = {10.1038/nm.3589}, pmcid = {PMC4087061}, pmid= {24952646} }
24952646

PMC4087061

10.1038/nm.3589

Abstract

"Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis(1,2). Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex(3,4). It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the beta(3)-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe(-/-) mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans."

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For attribution in academic contexts, please cite this work as:

Heidt, T., Sager, H. B., Courties, G., Dutta, P., Iwamoto, Y., Zaltsman, A., von zur Muhlen, C., Bode, C., Fricchione, G. L., Denninger, J., Lin, C. P., Vinegoni, C., Libby, P., Swirski, F. K., Weissleder, R., & Nahrendorf^#, M. (2014). Chronic variable stress activates hematopoietic stem cells. Nature Medicine, 20(7), 754–758. https://doi.org/10.1038/nm.3589