Neural Regulation of Hematopoiesis, Inflammation, and Cancer
Open accessAbstract
Although the function of the autonomic nervous system (ANS) in mediating the flight-or-fight response was recognized decades ago, the crucial role of peripheral innervation in regulating cell behavior and response to the microenvironment has only recently emerged. In the hematopoietic system, the ANS regulates stem cell niche homeostasis and regeneration and fine-tunes the inflammatory response. Additionally, emerging data suggest that cancer cells take advantage of innervating neural circuitry to promote their progression. These new discoveries outline the need to redesign therapeutic strategies to target this underappreciated stromal constituent. Here, we review the importance of neural signaling in hematopoietic homeostasis, inflammation, and cancer.
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Bone marrow has dense sympathetic innervation that helps mobilize leukocytes into circulation during stress and under homeostatic conditions.
“It is well established that bone marrow receives dense sympathetic innervation, which contributes to the mobilization of leukocytes into circulation during stress or under homeostatic conditions60,61.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [60]
The Introduction (page unavailable) says bone marrow is highly innervated by sympathetic nerves and that circadian neural signals influence leukocyte trafficking. The section “Autonomic regulation of hematopoietic homeostasis” (page unavailable) links sympathetic signaling to release of hematopoietic stem and progenitor cells into peripheral blood, both rhythmically and after G-CSF treatment. It does not establish the broader claim that this innervation mobilizes leukocytes into circulation during stress and under homeostatic conditions. (LLM, conf=0.84)
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References 161 · Cited by 265
Research works printed but not linked: 2
- LIEBIG C AYALA G WILKS JA BERGER DH ALBO D 2009b Perineural invasion in cancer: a review of the literature Cancer 115 3379 91 19484787
- PALM D ENTSCHLADEN F 2007 Neoneurogenesis and the Neuro-Neoplastic Synapse Prog Exp Tumor Res 39 91 98 17314503
- Authors
- Hanoun, M., Maryanovich, M., Arnal-Estapé, A., & Frenette, P. S.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Frenette, Paul S.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 86
- Issue
- 2
- Pages
- 360-373
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4416657
- OpenAlex
- W1987703447
- Cited by
- 265
- References
- 161
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 33 · 2023: 20 · 2022: 23 · 2021: 36 · 2020: 28 · 2019: 26 · 2018: 21 · 2017: 14 · 2016: 21 · 2015: 4
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Funders
- New York State Department of Health (C029154)
- Leukemia and Lymphoma Society
- New York State Stem Cell Science (C029154)
- European Commission (EMBOCOFUND2012, 600394)
- Deutsche Forschungsgemeinschaft (Ha 6731/1-1)
- Weizmann Institute of Science
- National Institutes of Health (C029154)
- National Heart, Lung, and Blood Institute (HL069438, R01HL116340, R01HL069438, HL116340)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056638, DK056638)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- autonomic nervous system, hematopoiesis, hematopoietic niche, inflammation, cancer, peripheral innervation, neural regulation, tumor microenvironment, hematopoietic regeneration, neuronal signaling
- MeSH terms
- Autonomic Nervous System, Autonomic Nervous System Diseases, Bone Marrow, Depression, Hematopoiesis, Homeostasis, Humans, Inflammation, Leukemia, Myeloid, Neoplasms, Neuropeptides, Stress, Psychological, Comorbidity, Survival Rate, Neurotransmitter Agents
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