ATP from sensory neuron-interneuron crosstalk is key to spreading inflammation in rheumatoid arthritis

Summary: In rheumatoid arthritis, inflammation in one joint is transferred to other joints through the sensory neuron connections in the spinal cord, leading to inflammation in the other joints. Inflammation in one joint led to an increase in ATP in other joints, which led to an increase in a signaling molecule that led to inflammation. Blocking the pathway reduced the spread of inflammation.

Source: University of Hokkaido

Rheumatoid arthritis is a chronic inflammatory autoimmune disease that primarily affects joints. One of the main features of this disease is distant inflammation, where the inflammation spreads from one joint to another.

Research has shown that neural circuits, or cells that have migrated from the joints, are involved in the spread of inflammation, but the detailed mechanism by which this happens has not been elucidated.

A team of researchers from Japan and the US, led by Professor Masaaki Murakami of Hokkaido University, has revealed that distant inflammation spreads through neuronal crosstalk and that adenosine triphosphate (ATP) plays a key role in this process.

Their findings, published in the Journal of Experimental Medicinemay lead to new therapies and treatments for inflammatory diseases.

Inflammation is part of the natural immune response that occurs in response to infection or irritation. It is a process in which the immune system, involving immune cells, blood vessels and molecular mediators, tries to clear the pathogens and damaged cells and then repair the damage.

However, excessive inflammation is a condition in itself and is seen in diseases such as hay fever, atherosclerosis, psoriasis and rheumatoid arthritis.

In this study, the authors used previous observations of the gateway reflex — an immune response mechanism in which specific neural signals alter the state of specific blood vessels to allow immune cells to invade tissue, leading to local inflammation — to hypothesize that neural crosstalk could be responsible for inflammation. at a distance.

Rheumatoid arthritis is a chronic inflammatory autoimmune disease that primarily affects joints. Image is in the public domain

They tested this hypothesis through experiments in rheumatoid arthritis models in mice. The mice were divided into control and test groups. In the test groups, the sensory neural circuits between the left and right ankle joints were interrupted. Arthritis of the left ankle was then induced in both sets of mice and the spread of arthritis to the right ankle was observed.

Their results showed that the inflammatory signal in one joint is transferred via a sensory neuron connection through the spinal cord, leading to inflammation in both joints. Specifically, inflammation in one joint led to an increase in ATP in both joints, which led to an increase in a signaling molecule that resulted in inflammation. Blocking this pathway prevented the spread of inflammation.

Since this study was conducted in mouse models, it is necessary to determine whether the findings apply to rheumatoid arthritis and other chronic inflammatory diseases in humans. If so, it could be a therapeutic target for several diseases with spreading inflammation.

About this research news on inflammation and rheumatoid arthritis

Writer: press office
Source: University of Hokkaido
Contact: Press Office – Hokkaido University
Image: The image is in the public domain

Original research: Closed access.
“ATP spreads inflammation to other limbs through crosstalk between sensory neurons and interneurons” by Rie Hasebe et al. Journal of Experimental Medicine


Abstract

Also see

This shows an old man walking

ATP spreads inflammation to other limbs through crosstalk between sensory neurons and interneurons

Neural circuits between lesions are a mechanism by which local inflammation spreads to distant positions.

Here we show that the inflammatory signal is propagated from one side of the joint to the other via sensory neuron-interneuron crosstalk, with ATP in the nucleus.

Surgical ablation or pharmacological inhibition of this neural pathway prevented the development of inflammation on the other hand.

Mechanistic analysis showed that ATP serves as both a neurotransmitter and an inflammation enhancer, thus acting as an intermediary between the local inflammation and the neural pathway that induces inflammation on the other side.

These results suggest that blockade of this neural pathway, termed the external inflammation gateway reflex, may have therapeutic value for inflammatory diseases, particularly those, such as rheumatoid arthritis, where the inflammation spreads to distant positions.

Leave a Comment