Researchers at Columbia University’s Zuckerman Institute have discovered that the brain has an astonishing ability to regulate the immune system. This study, carried out in mice, revealed that the brain can both detect inflammation and modulate the immune response, either speeding it up or suppressing it if necessary. This discovery could pave the way for new therapies to treat a range of diseases in which the immune system becomes overactive or dysregulated.
The researchers were motivated by a fundamental question: To what extent does the brain control the body’s immune responses? Motivation stems from previous work suggesting that the brain and body communicate largely through a pathway known as the brain-body axis.
Previous studies hinted at this interaction but did not fully explore the mechanisms or extent of the brain’s involvement in managing the immune system. The team aimed to uncover these connections and understand how the brain monitors and regulates inflammatory responses, a function essential for maintaining health.
“We discovered all these ways that the body informs the brain about its current state,” said Mengtong Li, co-first author and postdoctoral researcher. “We wanted to understand how far the brain’s knowledge and control over the body’s biology extends.”
To study the role of the brain in immune regulation, scientists conducted experiments on mice. They focused on the caudal nucleus of the solitary tract (cNST), a region of the brainstem heavily involved in the brain-body communication pathway. The cNST is the primary target of the vagus nerve.
Researchers used a bacterial compound called lipopolysaccharide (LPS) to trigger an immune response in mice. This compound is known to activate the innate immune system, the body’s first line of defense against pathogens. They then measured the levels of various immune molecules in the mice, both pro-inflammatory and anti-inflammatory.
To understand the role of cNST, researchers chemically manipulated its activity. They used advanced techniques to suppress or activate cNST neurons in response to LPS challenge. They also identified specific groups of neurons within the cNST and vagus nerve that are involved in the detection and control of inflammation.
The study found that the brain, particularly the cNST, significantly influences the body’s inflammatory responses. When the researchers suppressed cNST activity, they observed an uncontrollable inflammatory response: levels of pro-inflammatory molecules spiked, while anti-inflammatory molecules plummeted. Conversely, when they activated the cNST, the inflammatory response was attenuated, with pro-inflammatory molecules significantly decreasing and anti-inflammatory molecules significantly increasing.
“The brain is the center of our thoughts, emotions, memories and feelings,” said Hao Jin, co-first author of the published study. “Thanks to tremendous advances in circuit tracing and single-cell technology, we now know that the brain does much more than that. It monitors the functioning of each system in the body.
This indicates that cNST acts as a thermostat for the immune system, helping to maintain a balanced response to inflammation. The researchers also identified specific neurons in the vagus nerve and cNST that are crucial for detecting and controlling inflammation. These neurons respond to different immune signals, including pro-inflammatory and anti-inflammatory cytokines, which are molecules that signal immune responses.
Although these results are promising, the study has several limitations. First, the research was conducted in mice, and while there are similarities between mouse and human biology, further studies are needed to confirm that the same mechanisms work in humans. Additionally, the study focused primarily on the innate immune system, which responds quickly to threats but lacks the memory capabilities of the adaptive immune system. How the brain might influence adaptive immunity remains an open question.
Nevertheless, the implications of this study are considerable. If similar mechanisms were discovered in humans, it could revolutionize the way we treat various immune-related diseases. Conditions such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease, which are currently managed but not cured, could benefit from therapies targeting the brain’s control of inflammation.
This discovery could also lead to new treatments for acute inflammatory conditions, such as the severe immune reactions seen in certain viral infections, including COVID-19. The ability to modulate the immune system through the brain opens a new field of possibilities in medical treatment, offering hope for better management and perhaps even cures for chronic and acute inflammatory diseases.
“This new discovery could provide an exciting therapeutic avenue for controlling inflammation and immunity,” said Charles S. Zuker, senior author of the study, a principal investigator at Columbia’s Zuckerman Institute and a Howard Hughes Medical researcher. Institute.
The study titled “A brain-body circuit that regulates the body’s inflammatory responses” was authored by Hao Jin, Mengtong Li, Eric Jeong, Felipe Castro-Martinez and Charles S. Zuker.
News Source : www.psypost.org
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