Active Bones, Joints & Muscles

How do sympathetic neurons interact with immune cells to mediate inflammation and pain in rheumatoid arthritis?

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

In rheumatoid arthritis, the sympathetic nervous system—the network of nerves that controls the body’s fight-or-flight response—may be actively driving joint inflammation and pain, not just reacting to it. Many patients continue to suffer even when standard treatments tamp down immune activity, suggesting something else is at play. This project aims to map exactly how sympathetic neurons talk to immune cells, blood vessels, and sensory nerves to worsen the disease. The researchers will mine existing gene-expression data to identify the molecular handshakes—ligand-receptor pairs—between neurons and immune cells. They will then grow human sympathetic neurons from stem cells in the lab and expose them to immune cells taken from rheumatoid arthritis patients’ blood and joint fluid, watching how the cells change. They will also create miniature blood vessel and sensory nerve tissues to see how sympathetic signals alter blood flow and pain perception. Finally, they will test whether activating the sympathetic system causes fluid to leak from blood vessels in mice. This is fundamental science. If successful, it will provide the first detailed map of how the sympathetic nervous system contributes to rheumatoid arthritis in humans. That map could eventually point to new drug targets—perhaps drugs that block specific nerve-immune conversations—offering relief for patients who do not respond to current therapies.

View original technical description
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by joint inflammation and destruction. Many patients experience persistent inflammation and pain despite treatment. Evidence suggests a role for sympathetic nervous system (SNS) in RA pathology. We aim to address how sympathetic neurons interact with immune cells, blood vessels and sensory neurons to delineate how SNS influences inflammation and pain in RA. We will analyse published transcriptomic sympathetic neuron and immune cell datasets to uncover ligand-receptor pairs that contribute to inflammation and pain. We will differentiate human iPSC-derived sympathetic neurons and investigate how they influence phenotypes of immune cells isolated from RA patients’ blood or synovial fluid. We will interfere with ligand-receptor pairs identified by bioinformatic analysis in vitro to validate their significance. We will differentiate iPSC-derived blood vessel organoids and iPSC-derived sensory neurons to assess how SNS activity affects vascular processes and how crosstalk between sympathetic and sensory neurons affects immune cell phenotypes. We will investigate how SNS activation affects plasma extravasation using mice. This project will provide an unprecedented understanding of how SNS activity contributes to RA pathology in humans and may suggest novel therapeutic strategies. Key words: rheumatoid arthritis, sympathetic nervous system, inflammation, pain

View the original record at the funder ↗

Researchers

Trishalee Gungoosingh (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Bi-directional communication between neurons, immune and stromal cells in rheumatoid arthritis
Manipulation of monocytes/macrophages for the control of arthritis pain using pro-resolving lipid mediators and blockade of CX3CR1 receptor
Exploring the role of the immune system in maladaptive pain sensitisation
Trafficking and regulation of immune cells between the blood, skin and joint in autoimmune rheumatic disease.
Identifying synovial tissue biomarkers and mechanisms of transition from pre-clinical RA to RA.

Original classification

PhD Studentship (Basic)

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