Immune System Affects Body and Mind

A study from the Washington University School of Medicine has shown that a molecule which is produced by the immune system acts on the brains of mice to change behavior. The evidence illuminates a surprising body-mind connection.

The research team found that in mice, immune cells surrounding the brain produce a molecule that is then absorbed by brain neurons where it seems to be necessary for normal behavior. The findings indicate that elements of the immune system affect both body and mind and that the immune molecule known as IL-17 may be the link between the two.

The team notes that the brain and the body are not as separate as many people think. What they found is that the immune molecule IL-17 is produced by immune cells that reside in areas around the brain. These molecules could affect brain function through interactions with neurons to influence anxiety-like behaviors in mice. The team is now looking at whether too little or too much of IL-17 could be tied to anxiety in people.

IL-17 is a cytokine which is a signaling molecule that assists in orchestrating the immune response to infection through activating and directing immune cells. It has also be tied to autism in animal studies and also depression in people.

However, it is something of a mystery how the IL-17 molecule might influence brain disorders. Much of an immune system in the brain and a few immune cells that reside there do not produce IL-17. The tissues surrounding the brain are teeming with immune cells and among them a small population known as gamma-delta T cells that produce the immune molecule IL-17.

The research team set out to determine if gamma-delta T cells near the brain have an impact on behavior. Using mice, the team discovered that the meninges are rich in gamma-delta T cells and these cells under normal conditions continually produce IL-17, filling the tissues around the brain with IL-17.

To determine if gamma-delta T cells or IL-17 affect behavior, the team put the study mice through established tests of social behavior, memory, anxiety and foraging. The mice that lacked gamma-delta T cells or IL-17 were indistinguishable from mice who had normal immune systems on all measures except anxiety.

In the wild, open fields keep mice exposed to predators such as hawks and owls. They have therefore evolved a fear of open spaces. The team conducted two separate tests which involved giving mice the option of entering exposed areas. The mice with normal amounts of IL-17 and gamma-delta T cells kept mostly to the enclosed and more protective edges during the tests. The mice without IL-17 and gamma-delta T cells ventured into the open spaces. The team interpreted this lapse of vigilance as decreased anxiety.

Additionally, the team discovered that neurons in the brain have receptors on their surfaces that will respond to IL-17. When these receptors were removed so that the neurons could not detect the presence of IL-17, the mice indicated less vigilance. The team says these findings suggest that behavioral changes are not a byproduct but instead an important and integral part of neuro-immune communication.

The team did not expose the study mice to viruses or bacteria to study the effects of infection directly. They did however, inject the animals with lipopolysaccharide which is a bacteria product that elicits a strong response from the immune system. Gamma-delta T cells in the tissues surrounding the mice’s brains produced more IL-17 in response to the injection. However, when the animals were then treated with an antibiotic the amount of IL-17 was decreased. This suggests the gamma-delta T cells could detect the presence of normal bacteria such as those found in the gut microbiome as well as invading bacterial species, and appropriately respond to regulate behavior.

The team suggests that the link between the immune system and the brain may have evolved in a multi-pronged survival strategy. Increased vigilance and alertness could help rodents survive an infection through discouraging behaviors that increase the risk of predation or further infection while in a weakened state.

They believe the immune system and the brain have most likely evolved together. Selecting special molecules such as IL-17 to protect us behaviorally and immunologically, is a smart way to protect against infection. This is a great example of how cytokines which have evolved to fight against pathogens are also acting on the brain and modulating behavior.

The research team is now studying how gamma-delta T cells in the meninges detect bacterial signals that come from other parts of the body. They are also investigating how IL-17 signaling in neurons translates into changes in behavior.

To view the original scientific study click below

T cells regulate anxiety-like behavior via IL-17a signaling in neurons. Nature Immunology, 2020; DOI: 10.1038/s41590-020-0776-4