Neuropeptide substance P and the immune response
Open accessAbstract
Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.
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SP has been reported to be a potent neuroimmunomodulator functioning through NK1R, which is widely expressed in immune cells.
“Functioning through NK1R, which is widely expressed in immune cells, SP has been reported to be a potent neuroimmunomodulator78.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [78]
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Hallmarks of peripheral nerve function in bone regeneration
Tao, R., Mi, B., Hu, Y., Lin, S., Xiong, Y., Lu, X., Panayi, A. C., Li, G., & Liu, G. (2023) · Bone Research · doi:10.1038/s41413-022-00240-x · Cited by 110 · see citing works
Yan, D., Liu, X., & Guo, S.-W. (2019) · Scientific Reports · doi:10.1038/s41598-019-39170-w · Cited by 82 · see citing works
Hatziagelaki, E., Adamaki, M., Tsilioni, I., Dimitriadis, G., & Theoharides, T. C. (2018) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.250845 · Cited by 62 · see citing works
- Authors
- Mashaghi, A., Marmalidou, A., Tehrani, M., Grace, P. M., Pothoulakis, C., & Dana, R.
- Affiliations
- Massachusetts Eye and Ear Infirmary (US)
- University of Colorado Boulder (US)
- University of California, Los Angeles (US)
- Corresponding author
- Dana, Reza
- ORCID
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2016-06-17
- Volume
- 73
- Issue
- 22
- Pages
- 4249-4264
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC5056132
- OpenAlex
- W2442224165
- Cited by
- 493
- References
- 258
- Citations by year
- 2026: 61 · 2025: 56 · 2024: 53 · 2023: 73 · 2022: 64 · 2021: 65 · 2020: 53 · 2019: 29 · 2018: 20 · 2017: 16 · 2016: 1
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Foundation for the National Institutes of Health (R01 DK047343, EY020889, EY012963)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- substance P, neuropeptides, immune response, neuroimmune interactions, neurokinin-1 receptor, cytokine production, immune cell proliferation, inflammation, nociception, paracrine signaling, hormone signaling, immune cell mobilization
- MeSH terms
- Amino Acid Sequence, Animals, Disease, Humans, Immunity, Substance P, Signal Transduction, Immunomodulation
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 ›
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