The immune system affects the mind and body, the study indicates

Neurons (green) in the mouse brain have a receptor (cyan) that detects the immune molecule IL-17. Researchers at Washington University School of Medicine in St. Louis have discovered that a molecule produced by the immune system acts on the brain to change the behavior of mice. Sincerely: Washington University School of Medicine

New research at Washington University School of Medicine in St. Louis helps illuminate the amazing mind-body connection. In mice, researchers found that immune cells around the brain produce a molecule that is subsequently absorbed by neurons in the brain, where it appears to be essential for normal behavior.

Conclusion, published in September 14 Nature immunology, Indicate that elements of the immune system affect both the mind and body, and that the immune molecule IL-17 may be an important link between the two.

Senior author Jonathan Kipnis, PhD, Alan A. and Edith L. “The brain and body are not as different as people think,” said Wolff Definitive Professor of Pathology and Immunology and a professor of neurology and professor of neurosurgery. Of neuroscience. “What we found here is that an immune molecule — IL-17 — is produced by immune cells living in areas around the brain, and that interact with neurons to affect anxiety-like behavior in mice. The medium can affect brain function. We now see that very little or very little of IL-17 may be associated with anxiety in people. ”

IL-17 is a cytokine, a signaling molecule that enhances the immune response to infection by activating and directing immune cells. IL-17 has also been linked to autism in animals and depression in people.

How an immune molecule like IL-17 can affect brain disorders, however, is a mystery because the brain does not have much immune system and some immune cells that reside there do not produce IL-17. Huh. But Kipnis, along with the first author and postdoctoral researcher Kalil Elwes de Lima, PhD, realized that the tissue innervating the brain was teeming with immune cells, among them, a small population known as gamma catabolic T cells. Produces IL. 17. They determine whether to have an effect on the behavior of gamma-delta T cells near the brain. Kipnis and Alves de Lima did research at the University of Virginia University of Medicine; Both are now at the University of Washington.

Using mice, they found that the meninges are enriched in gamma-delta T cells and that such cells, under normal conditions, consistently produce IL-17, filling the tissue surrounding the brain with IL-17.

To determine whether gamma-delta T cells or IL-17 affect behavior, Alves de Lima placed mice through established tests of memory, social behavior, foraging, and anxiety. Mice that lacked gamma-delta T cells or IL-17 were indistinguishable from mice with a normal immune system on all immunity or anxiety. In the wild, open fields release mice exposed to predators such as owls and eagles, to create fear of open spaces. The researchers conducted two separate tests, in which mice were given the option to enter exposed areas. While mice with normal amounts of gamma-delta T cells and IL-17 levels mostly placed themselves in more protective edges and enclosed areas during testing, mice without gamma-delta T cells or IL-17 in open areas. There is a lack of vigilance that the researchers downplayed anxiety.

In addition, scientists found that neurons in the brain have receptors on their surfaces that respond to IL-17. When scientists removed those receptors so that neurons could not detect the presence of IL-17, the mice showed less alertness. Researchers say the findings suggest that behavioral change is not a byproduct, but an integral part of neuro-immune communication.

Although researchers did not expose mice to bacteria or viruses to study the effects of the infection, they injected the animals with lipopolysaccharide, a bacterial product that elicited a strong immune response. Gamma-delta T cells in tissues around the brain of mice produced more IL-17 in response to injection. When the animals were treated with antibiotics, however, the amount of IL-17 was reduced, suggesting gamma-delta T cells that could have sensed the presence of normal bacteria such as gut microbiomes. Are, as well as attack species of bacteria, and react appropriately to regulate behavior.

Researchers hypothesize that the link between the immune system and the brain may develop as part of a multi-layered survival strategy. Alves de Lima stated that increased vigilance and vigilance can help avoid behaviors that discourage behavior, which further increases the risk of infection or predation.

“The immune system and brain are most likely developed,” Alves de Lima said. “Selecting particular molecules to protect us immunologically and practically at the same time is a smart way to protect against infection. This is a good example of how cytokines, which originally evolved to fight pathogens, are the brain. And also working on actionable behavior. ”

Researchers are now studying how gamma-delta T cells in meninges detect bacterial signals from other parts of the body. They are also investigating how IL-17 signaling in neurons is altered by behavioral changes.

Identified subtype and developmental pathways of innate T cells

more information:
Alves de Lima K, et al. Meningeal ening T cells regulate anxiety-like behavior in neurons via IL-17a signaling. Nature immunology. September 14, 2020. DOI: 10.1038 / s41590-020-0776-4

Provided by Washington University School of Medicine

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