Scientists at Washington University School of Medicine found a strong connection between body and mind. The body’s immune cells surround the brain; a few produce a molecule called interleukin-17 (IL-17).
Nerve cells in the brain absorb the molecule and play an essential component for normal behavior—the findings are published on Sept. 14 in Nature Immunology (Alves de Lima et al. 2020)
“What we’ve found here is that an immune molecule, interleukine-17 (IL-17), is produced by immune cells residing in areas around the brain, and it could affect brain function through interactions with neurons to influence anxiety-like behaviors in mice. We are now looking into whether too much or too little of IL-17 could be linked to anxiety in people,” stated Jonathan Kipnis, the paper’s senior author.
IL-17 is a cytokine, a signaling molecule that modulates the immune response to infection (Curtis et al. 2009). Elevated IL-17 also has been linked to autism in children (Al-Ayadhi et al. 2012) and causes depression-like symptoms in animals (Nadeem et al. 2017).
However, the mechanism is a mystery, how an immune molecule like IL-17 t influence brain functions since the brain does not have any developed immune system. Even the immune cells that do reside in the brain don’t produce IL-17.
In the study, the researchers found that gamma delta T cells that produce IL-17 exist in the tissues surrounding the brain. Then, they investigated if the gamma-delta T cells have an impact on behavior.
Using mice, they discovered that the layers that enclose the brain are rich in gamma-delta T cells that continually produce IL-17, filling the tissues surrounding the brain with IL-17 in normal conditions.
To determine whether gamma-delta T cells or IL-17 affect behavior, the researchers put 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 normal immune systems on all measures except anxiety.
Usually, mice fear open space because of predators such as owls and hawks. The researchers conducted two separate tests that involved giving mice the option of entering open areas.
They found that the mice with normal amounts of gamma-delta T cells and levels of IL-17 kept themselves mostly in protective areas during the tests. On the other hand, mice without gamma-delta T cells or IL-17 entered the open spaces, a sign of less vigilance that the researchers interpreted as decreased anxiety.
Moreover, the scientists discovered that neurons in the brain have receptors on their surfaces that respond to IL-17. When the receptors were removed from the receptor so that the neurons could not detect IL-17, the mice showed less vigilance. The researchers say the findings suggest that behavioral changes are not a byproduct but an integral part of neuro-immune communication.
To investigate the effects of infection, they injected the animals with lipopolysaccharide, a bacterial product that elicits a strong immune response. They observed that gamma-delta T cells in the tissues around the mice’s brains produced more IL-17 in response to the injection.
The researchers speculate that the link between the immune system and the brain could have evolved as a part of a multipurpose survival strategy.
The researchers now are studying how gamma-delta T cells in the meninges detect bacterial signals from other parts of the body. They also are investigating how IL-17 signaling in neurons translates into behavioral changes.