Vasopressin drives aberrant myeloid differentiation of hematopoietic stem cells, contributing to depression in mice
Open accessAbstract
Psychological stress is often linked to depression and can also impact the immune system, illustrating the interconnectedness of mental health and immune function. Hematopoietic stem cells (HSCs) can directly sense neuroendocrine signals in bone marrow and play a fundamental role in the maintenance of immune homeostasis. However, it is unclear how psychological stress impacts HSCs in depression. Here, we report that neuroendocrine factor arginine vasopressin (AVP) promotes myeloid-biased HSC differentiation by activating neutrophils. AVP administration increases neutrophil and Ly6C hi monocyte production by triggering HSCs that rely on intrinsic S100A9 in mice. When stimulated with AVP, neutrophils return to the bone marrow and release interleukin 36G (IL-36G), which interacts with interleukin 1 receptor-like 2 (IL-1RL2) on HSCs to produce neutrophils with high Elane expression that infiltrate the brain and induce neuroinflammation. Together, these findings define HSCs as a relay between psychological stress and myelopoiesis and identify the IL-36G-IL-1RL2 axis as a potential target for depression therapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Adrenalectomy-model mice fail to exhibit the typical stress-induced immune cell mobilization response, characterized by lymphocyte suppression and myeloid cell expansion.
“These results suggest that adrenalectomy-model mice fail to exhibit the typical stress-induced immune cell mobilization response, which is characterized by lymphocyte suppression and myeloid cell expansion [3,17,42].”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [42]
Cites
Otte, C., Gold, S. M., Penninx, B. W., Pariante, C. M., Etkin, A., Fava, M., Mohr, D. C., & Schatzberg, A. F. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.65 · Cited by 2,269 · see citing works
Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Krashes, M. J., Koda, S., Ye, C., Rogan, S. C., Adams, A. C., Cusher, D. S., Maratos-Flier, E., Roth, B. L., & Lowell, B. B. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46229 · Cited by 1,578 · see citing works
Chronic variable stress activates hematopoietic stem cells
Heidt, T., Sager, H. B., Courties, G., Dutta, P., Iwamoto, Y., Zaltsman, A., von zur Muhlen, C., Bode, C., Fricchione, G. L., Denninger, J., et al. (2014) · Nature Medicine · doi:10.1038/nm.3589 · Cited by 803 · see citing works
Fundamental properties of unperturbed haematopoiesis from stem cells in vivo
Busch, K., Klapproth, K., Barile, M., Flossdorf, M., Holland-Letz, T., Schlenner, S. M., Reth, M., Höfer, T., & Rodewald, H.-R. (2015) · Nature · doi:10.1038/nature14242 · Cited by 769 · see citing works
Bogeska, R., Mikecin, A.-M., Kaschutnig, P., Fawaz, M., Büchler-Schäff, M., Le, D., Ganuza, M., Vollmer, A., Paffenholz, S. V., Asada, N., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.06.012 · Cited by 299 · see citing works
Peripheral Blood Cell–Stratified Subgroups of Inflamed Depression
Lynall, M.-E., Turner, L., Bhatti, J., Cavanagh, J., de Boer, P., Mondelli, V., Jones, D., Drevets, W. C., Cowen, P., Harrison, N. A., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.11.017 · Cited by 187 · see citing works
Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression
Issler, O., van der Zee, Y. Y., Ramakrishnan, A., Wang, J., Tan, C., Loh, Y.-H. E., Purushothaman, I., Walker, D. M., Lorsch, Z. S., Hamilton, P. J., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.03.023 · Cited by 156 · see citing works
Peripheral blood cellular immunophenotype in depression: a systematic review and meta-analysis
Foley, É. M., Parkinson, J. T., Mitchell, R. E., Turner, L., & Khandaker, G. M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01919-7 · Cited by 138 · see citing works
Säwen, P., Eldeeb, M., Erlandsson, E., Kristiansen, T. A., Laterza, C., Kokaia, Z., Karlsson, G., Yuan, J., Soneji, S., Mandal, P. K., et al. (2018) · eLife · doi:10.7554/elife.41258 · Cited by 120 · see citing works
Inflammatory signaling regulates hematopoietic stem and progenitor cell development and homeostasis
Collins, A., Mitchell, C. A., & Passegué, E. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201545 · Cited by 111 · see citing works
HCN2 Channels in Cholinergic Interneurons of Nucleus Accumbens Shell Regulate Depressive Behaviors
Cheng, J., Umschweif, G., Leung, J., Sagi, Y., & Greengard, P. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.018 · Cited by 110 · see citing works
Carvalho, A. F., Cavalcante, J. L., Castelo, M. S., & Lima, M. C. O. (2007) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.2007.00846.x · Cited by 110 · see citing works
Fang, X., Jiang, S., Wang, J., Bai, Y., Kim, C. S., Blake, D., Weintraub, N. L., Lei, Y., & Lu, X.-Y. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-01004-x · Cited by 95 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Yang, J., Jia, Y., Guo, T., Zhang, S., Huang, J., Lu, H., Li, L., Xu, J., Liu, G., & Xiao, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136063 · Cited by 11 · see citing works
“These results suggest that adrenalectomy-model mice fail to exhibit the typical stress-induced immune cell mobilization response, which is characterized by lymphocyte suppression and myeloid cell expansion [3,17,42].”
- Authors
- Mou, R., Ma, J., Ju, X., Wu, Y., Chen, Q., Li, J., Shang, T., Chen, S., Yang, Y., Li, Y., Lv, K., Chen, X., Zhang, Q., Liang, T., Feng, Y., & Lu, X.
- Affiliations
- First Affiliated Hospital Zhejiang University (CN)
- Hangzhou Seventh Peoples Hospital (CN)
- Hangzhou Normal University (CN)
- Sir Run Run Shaw Hospital (CN)
- Ningbo University (CN)
- Women's Hospital, School of Medicine, Zhejiang University (CN)
- Hunan University (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Corresponding author
- Feng, Ye
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2024-12
- Volume
- 31
- Issue
- 12
- Pages
- 1794-1812.e10
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W4403638951
- Cited by
- 20
- References
- 13
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 2
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Zhejiang Province Natural Science Foundation (LZ23C110001)
- Deutsches Krebsforschungszentrum
- Zhejiang Provincial Ten Thousand Plan for Young Top Talents
- National Natural Science Foundation of China (82471905, 82072241)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- vasopressin, depression, hematopoietic stem cells, myeloid differentiation, psychological stress, neutrophils, S100A9, neutrophil elastase, neuroinflammation, myelopoiesis, neuroendocrine-immune interaction
- MeSH terms
- Animals, Arginine Vasopressin, Cell Differentiation, Depression, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Neutrophils, Stress, Psychological, Myeloid Cells, Myelopoiesis, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
