Social Stress Mobilizes Hematopoietic Stem Cells to Establish Persistent Splenic Myelopoiesis
Open accessAbstract
Psychosocial stress accelerates myelopoietic production of monocytes and neutrophils that contributes to a variety of health complications ranging from atherosclerosis to anxiety. Here, we show that social stress in mice mobilizes hematopoietic stem progenitor cells (HSPCs) from the bone marrow that enter circulation, engraft into the spleen, and establish a persistent extramedullary hematopoietic depot. These splenic progenitors actively proliferate and differentiate into multiple cell types, including monocytes, neutrophils, and erythrocytes. Splenic erythropoiesis partially abrogates stress-induced anemia. Repeated injection with isoprenaline induces progenitor mobilization to the spleen, identifying a key role for β-adrenergic signaling. Moreover, protracted splenic production of CD11b + cells persists for at least 24 days after the cessation of social stress. Thus, chronic stress establishes a persistent extramedullary hematopoietic depot that can modify a wide range of chronic disease processes and alter homeostasis of the bi-directional regulatory axis between the nervous and immune systems.
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Mice exposed to CVS or CSDS show expansion of myeloid progenitor cells and reduced lymphoid progenitors.
“Specifically, mice exposed to either CVS or CSDS exhibit an expansion of myeloid progenitor cells, along with a downregulation of lymphoid progenitors33,59.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [59]
The Results sections report increased myeloid progenitor colony-forming units after repeated social defeat stress, alongside reduced lymphocyte proportions in bone marrow and blood. They do not establish a reduction in lymphoid progenitors. The Introduction mentions increased myeloid cell production under chronic variable stress, but does not report myeloid progenitor expansion or reduced lymphoid progenitors under that condition. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredChronic social stress in mice causes splenomegaly attributed to granulocyte accumulation and extramedullary myelopoiesis, which raises circulating monocyte levels.
“Chronic social stress in mice leads to splenomegaly, attributed to granulocyte accumulation and ectopic (or ‘extramedullary’) myelopoiesis, which consequently elevates circulating monocyte levels59,77.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [59]
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- Authors
- McKim, D. B., Yin, W., Wang, Y., Cole, S. W., Godbout, J. P., & Sheridan, J. F.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- The Ohio State University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Sheridan, John F.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 25
- Issue
- 9
- Pages
- 2552-2562.e3
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6342493
- OpenAlex
- W2902125411
- Cited by
- 153
- References
- 46
- Citations by year
- 2026: 18 · 2025: 13 · 2024: 23 · 2023: 18 · 2022: 21 · 2021: 22 · 2020: 17 · 2019: 19 · 2017: 1
- FWCI
- 10.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01-MH-093473, R01-MH097243)
- National Institute on Aging (R01-AG033028, R01-AG043404)
- National Institute of Dental and Craniofacial Research (T32-DE-014320)
- NIMH (F31-MH109234)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- social stress, hematopoietic stem cells, hematopoietic stem and progenitor cells, extramedullary hematopoiesis, splenic erythropoiesis, monocytes, neutrophils, beta-adrenergic signaling, isoproterenol, neuroimmune axis, chronic stress
- MeSH terms
- Cell Self Renewal, Anemia, Animals, Erythropoiesis, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Receptors, Adrenergic, beta, Spleen, Stress, Psychological, Signal Transduction, Lymphopoiesis, Myelopoiesis, Cell Proliferation
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