ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04256837 (Effect of Transcutaneous Electrical Auricular Stimulation of the Vagus Nerve in Kidney Transplant Recipients), which is not on this map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Transcutaneous Electrical Auricular Stimulation of the Vagus Nerve in Kidney Transplant Recipients
Who cites it
61 citing papers in PubMed, 129 citations in OpenAlex.
- In a secondary analysis from a randomised, double-blind placebo-controlled trial Dexmedetomidine blocks cholinergic dysregulation in delirium pathogenesis in patients with major surgery.Scientific reports · 2023Trial
- Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study.Arthritis research & therapy · 2015Trial
- Hepatic neurons and metabolically induced liver dysfunction.Nature reviews. Endocrinology · 2026Review
- Vagal neuropathies: An underrecognized potential driver of physical, mental, and immune symptoms.Brain, behavior, & immunity - health · 2026Review
- Effects of transcutaneous auricular vagus nerve stimulation or combined vagal and trigeminal nerve stimulation on platelet function and laboratory hemostasis parameters in healthy human subjects.Bioelectronic medicine · 2026Article
- The neuroimmune axis in cardiovascular disease: from immune activation to inflammatory resolution.Frontiers in immunology · 2026Review
- Vagus Nerve Regulation of Inflammatory Responses in Sepsis: Mechanistic Insights and Translational Applications.Journal of inflammation research · 2026Review
- Transcutaneous auricular vagus nerve stimulation for disorders of consciousness: a narrative review of neurophysiological mechanisms, clinical evidence, and future directions.Frontiers in human neuroscience · 2026Review
- CD200R1 modulates myelin phagocytosis and spleen response following spinal cord injury.Scientific reports · 2025Article
- Targeted spleen modulation: a novel strategy for next-generation disease immunotherapy.Theranostics · 2025Review
- Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- M1 cholinergic signaling in the brain modulates cytokine levels and splenic cell sub-phenotypes following cecal ligation and puncture.Molecular medicine (Cambridge, Mass.) · 2024Article
- Cholinergic signaling via the α7 nicotinic acetylcholine receptor regulates the migration of monocyte-derived macrophages during acute inflammation.Journal of neuroinflammation · 2024Article
- Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohn's Disease Patients: A Prospective Open-label Study.Journal of Crohn's & colitis · 2023Article
- Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice.Nature communications · 2023Article
- Increased Enzymatic Activity of Acetylcholinesterase Indicates the Severity of the Sterile Inflammation and Predicts Patient Outcome following Traumatic Injury.Biomolecules · 2023Article
- Transcutaneous auricular vagus nerve stimulation in the treatment of disorders of consciousness: mechanisms and applications.Frontiers in neuroscience · 2023Review
- Neuromodulation as a Potential Disease-Modifying Therapy for Osteoarthritis.Current rheumatology reports · 2023Review
- Crosstalk of nervous and immune systems in pancreatic cancer.Frontiers in cell and developmental biology · 2023Review
- The Effect of α7nAChR Signaling on T Cells and Macrophages and Their Clinical Implication in the Treatment of Rheumatic Diseases.Neurochemical research · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The cholinergic anti-inflammatory pathway is a physiological mechanism that inhibits cytokine production and diminishes tissue injury during inflammation. Recent studies demonstrate that cholinergic signaling reduces adhesion molecule expression and chemokine production by endothelial cells and suppresses leukocyte migration during inflammation. It is unclear how vagus nerve stimulation regulates leukocyte trafficking because the vagus nerve does not innervate endothelial cells. Using mouse models of leukocyte trafficking, we show that the spleen, which is a major point of control for cholinergic modulation of cytokine production, is essential for vagus nerve-mediated regulation of neutrophil activation and migration. Administration of nicotine, a pharmacologic agonist of the cholinergic anti-inflammatory pathway, significantly reduces levels of CD11b, a beta(2)-integrin involved in cell adhesion and leukocyte chemotaxis, on the surface of neutrophils in a dose-dependent manner and this function requires the spleen. Similarly, vagus nerve stimulation significantly attenuates neutrophil surface CD11b levels only in the presence of an intact and innervated spleen. Further mechanistic studies reveal that nicotine suppresses F-actin polymerization, the rate-limiting step for CD11b surface expression. These studies demonstrate that modulation of leukocyte trafficking via cholinergic signaling to the spleen is a specific, centralized neural pathway positioned to suppress the excessive accumulation of neutrophils at inflammatory sites. Activating this mechanism may have important therapeutic potential for preventing tissue injury during inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.