Reflex principles of immunological homeostasis
Open accessAbstract
The reasoning that neural reflexes maintain homeostasis in other body organs, and that the immune system is innervated, prompted a search for neural circuits that regulate innate and adaptive immunity. This elucidated the inflammatory reflex, a prototypical reflex circuit that maintains immunological homeostasis. Molecular products of infection or injury activate sensory neurons traveling to the brainstem in the vagus nerve. The arrival of these incoming signals generates action potentials that travel from the brainstem to the spleen and other organs. This culminates in T cell release of acetylcholine, which interacts with α7 nicotinic acetylcholine receptors (α7 nAChR) on immunocompetent cells to inhibit cytokine release in macrophages. Herein is reviewed the neurophysiological basis of reflexes that provide stability to the immune system, the neural- and receptor-dependent mechanisms, and the potential opportunities for developing novel therapeutic devices and drugs that target neural pathways to treat inflammatory diseases.
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Brain-to-gut signaling can directly affect the microbiota via the immune system or gut functions such as motility, release of neurotransmitters, and intestinal immune tone.
“brain to gut signaling can directly affect the microbiota, either via immune system or gut functions such as motility, release of neurotransmitters and intestinal immune tone (12, 17, 21, 31).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [31]
The Inflammatory Bowel Disease section (page unavailable) says vagus-nerve signaling may suppress cytokine release and inflammation locally in the bowel, supporting the immune-signaling part of the claim. It does not say that this changes the microbiota or identify gut motility or neurotransmitter release as routes by which brain-to-gut signaling affects it. (LLM, conf=0.84)
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- Authors
- Andersson, U., & Tracey, K. J.
- Affiliations
- Karolinska University Hospital (SE)
- Feinstein Institute for Medical Research (US)
- ORCID
- Tracey, Kevin J.
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2012-04-23
- Volume
- 30
- Issue
- 1
- Pages
- 313-335
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- PMC
- PMC4533843
- OpenAlex
- W2159374684
- Semantic Scholar
- 12990fd1d4c3d7010f06cbaec015f9c6e529bb15
- Cited by
- 414
- References
- 79
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 20 · 2023: 26 · 2022: 33 · 2021: 29 · 2020: 28 · 2019: 30 · 2018: 34 · 2017: 37 · 2016: 29 · 2015: 31 · 2014: 41 · 2013: 31 · 2012: 14
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM057226, R01GM062508)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- cholinergic anti-inflammatory pathway, immune homeostasis, vagus nerve, sensory neurons, brainstem, acetylcholine, alpha7 nicotinic acetylcholine receptor, T cells, macrophages, cytokine production, neuroimmune signaling, inflammatory diseases
- MeSH terms
- Acetylcholine, Animals, Anti-Inflammatory Agents, Homeostasis, Humans, Immunity, Innate, Inflammation, Neurons, Reflex, T-Lymphocytes
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.
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