Neuroimmune Interactions in Inflammatory Disorders

Within inflammatory disorders such as multiple sclerosis, autoimmune uveitis and systemic inflammatory diseases, bidirectional communication between the nervous and immune systems modulates disease onset, progression and resolution. Neural signals affect endothelial permeability at barrier interfaces and shape immune cell trafficking, while immune mediators influence neuronal excitability and synaptic plasticity. Central mechanisms involve specialised vascular structures— notably the blood–brain and blood–retina barriers—where neurally driven changes in endothelial cells and glial elements create selective entry points for autoreactive lymphocytes and myeloid cells. These processes are orchestrated by neurotransmitters, neuropeptides and cytokines, which collectively regulate barrier integrity, chemokine gradients and local inflammatory programmes. Emerging evidence highlights mechanosensory inputs, stress and sensory reflexes as critical modulators of regional immune access. Disruption or exaggeration of these neuroimmune circuits underlies the pathogenesis of diverse inflammatory disorders, and their manipulation offers promising therapeutic avenues.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Neuroimmune Interactions in Inflammatory Disorders publication trend

The graph below shows the total number of articles in neuroimmune interactions in inflammatory disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Gateway reflex: A neural mechanism whereby sensory or environmental stimuli induce local changes in vascular endothelium to permit immune cell infiltration into barrier tissues.

Blood–brain barrier (BBB): A selective endothelial interface that regulates the exchange of substances and immune cells between the bloodstream and the central nervous system.

Mechanotransduction: The process by which mechanical stimuli are converted into biochemical signals in neurons or other cells.

Chemokine: A chemotactic cytokine that directs migration of immune cells along concentration gradients.

Norepinephrine: A neurotransmitter released by sympathetic and sensory neurons that modulates vascular tone and immune responses.

References

1. Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit. eLife (2017).
2. The Gateway Reflex, a Novel Neuro-Immune Interaction for the Regulation of Regional Vessels. Frontiers in Immunology (2017).
3. A pain-mediated neural signal induces relapse in murine autoimmune encephalomyelitis, a multiple sclerosis model. eLife (2015).
4. The gateway reflex regulates tissue-specific autoimmune diseases. Inflammation and Regeneration (2024).
5. Gateway Reflex and Mechanotransduction. Frontiers in Immunology (2021).