The brain has the ability to control the immune system more than previously thought, with the capability of recognizing, increasing, and decreasing inflammation, as demonstrated by a recent study in mice conducted by researchers at Columbia’s Zuckerman Institute. “The brain is the center of our thoughts, emotions, memories and feelings,” said Hao Jin, PhD, a co-first author of the study published online today in Nature. Thanks to great advances in circuit tracking and singWith the advancements in cell technology, it has been found that the brain has a much more extensive role than previously believed. It actively monitors the function of every system in the body. Future research may lead to the discovery of drugs that can target this newly identified brain circuit, potentially providing treatment for a wide range of disorders and diseases related to immune system dysfunction. Charles S. Zuker, PhD, a principal investigator at Columbia’s Zuckerman Institute and a Howard Hughes Medical Institute investigator, stated that this new discovery could open up exciting opportunities for controlling inflammation and immunity. Ongoing work from the Zuker lab and other research groups is shedding light on the potential therapeutic applications of this finding.Emphasizing the significance of the body-brain axis, a crucial pathway that transmits information between the organs and the brain. Dr. Zuker and his team, for instance, determined that sugar and fat entering the gut utilize the body-brain axis to stimulate the desire and intense craving for sweet and high-fat foods.
“We identified numerous ways in which the body communicates with the brain regarding the body’s current condition,” explained co-first author Mengtong Li, PhD, a postdoctoral researcher in the Zuker lab. “We aimed to comprehend the extent of the brain’s understanding and regulation of the body’s biology.”
The researchers sought out potential links the brain may have.The article discusses the relationship between inflammation and innate immunity, which is the defense system that all animals share and is the oldest part of the immune system. While the adaptive immune system can remember previous encounters with intruders, the innate immune system attacks anything with common traits of germs. The simplicity of the innate immunity allows it to respond to new insults more quickly than the adaptive immunity.
Previous research in humans has shown that electrically stimulating the vagus nerve, which is a bundle of nerve fibers connecting the brain and the body’s internal organs, can have positive effects.The study suggests that the nervous system may be able to decrease the reaction associated with a specific molecule that causes inflammation. However, there are still many unanswered questions about how the body and brain interact in this system. For example, it is not clear how the brain affects the immune system and inflammatory response, how the body and brain communicate with each other, the neural pathways involved, and which components of the vagal and brain systems monitor and regulate inflammation.
To address these questions, the Zuker lab used a bacterial compound known to trigger innate immune responses. When this molecule was given to mice, it activated the caudal nucleus of the solitary tract, indicating a potential link between the molecule and the nervous system.The cNST, located in the brainstem, is a crucial part of the body-brain axis and is mainly affected by the vagus nerve.
Researchers demonstrated that blocking the cNST chemically led to an excessive inflammatory reaction to the immune challenge: the release of pro-inflammatory substances by the immune system was over three times the normal levels, while the levels of anti-inflammatory compounds were about three times lower than usual. On the other hand, stimulating the cNST artificially decreased the levels of pro-inflammatory substances by almost 70% and raised the levels of anti-inflammatory chemicals alm
The newly discovered brain circuit functions similar to a thermostat, assisting in regulating inflammatory responses to maintain a healthy body, according to Dr. Jin, who initiated the study as a postdoctoral researcher in Dr. Zuker’s lab and is now a tenure track investigator at the National Institute of Allergy and Infectious Diseases. Dr. Jin stated, “In hindsight, it is logical to have a master controller overseeing this crucial response.” Prior research on vagus nerve stimulation in humans suggests that the findings extend beyond mice, indicating potential implications in line with long-held beliefs on the significance of this discovery.
The connection between the mind and body is being studied by researchers. Dr. Jin mentioned that many psychosomatic effects may be related to the brain communicating with the body. The scientists have found specific groups of neurons in the vagus nerve and in the cNST that are involved in detecting and controlling pro- and anti-inflammatory activity. Dr. Zuker believes that this discovery provides new insights into how the brain monitors and influences body physiology. Finding ways to control this newly discovered brain circuit is now a focus of research.The development of new therapies for common autoimmune diseases, including rheumatoid arthritis, type I diabetes, multiple sclerosis, neurodegenerative diseases, lupus, inflammatory bowel disease, Crohn’s disease, long COVID syndrome, immune rejection of transplanted organs, and cytokine storms triggered by COVID infections, is now possible. According to a 2023 study published in The Lancet, autoimmune diseases may affect approximately one in 10 individuals. In the United States, the economic impact of autoimmune diseases is estimated to be around $100 billion annually, although this figure may actually be much higher.The Autoimmune Association is looking into utilizing the body-brain circuit to help manage a variety of immune system conditions. Drs. Jin and Li believe that by harnessing the activity of this circuit, they can effectively treat dysregulated inflammatory states in individuals with immune diseases and disorders.
