Study shows immune system affects mind, body
IL-17 is a cytokine, a signaling molecule that orchestrates the immune response to infection by activating and directing immune cells. IL-17 also has been linked to autism in animal studies and depression in people.
How an immune molecule like IL-17 might influence brain disorders is something of a mystery since there isn't much of an immune system in the brain and the few immune cells that do reside there don't produce IL-17, according to the researchers.
When the researchers realized that the tissues that surround the brain are teeming with immune cells, among them, a small population known as gamma delta T cells that produce IL-17, they set out to determine whether gamma-delta T cells near the brain have an impact on behavior.
Using mice, they discovered that the meninges are rich in gamma-delta T cells and that such cells continually produce IL-17, under normal conditions, filling the tissues surrounding the brain with IL-17.
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. The researchers conducted two separate tests that involved giving mice the option of entering exposed areas.
While the mice with normal amounts of gamma-delta T cells and levels of IL-17 kept themselves mostly to the more protective edges and enclosed areas during the tests, mice without gamma-delta T cells or IL-17 ventured into the open areas, a lapse of vigilance that the researchers interpreted as decreased anxiety.
Moreover, the researchers discovered that neurons in the brain have receptors on their surfaces that respond to IL-17. When they removed those receptors so that the neurons could not detect the presence of IL-17, the mice showed less vigilance.
The findings suggest that behavioral changes are not a byproduct but an integral part of neuro-immune communication.
Although the researchers did not expose mice to bacteria or viruses to study the effects of infection directly, they injected the animals with lipopolysaccharide, a bacterial product that elicits a strong immune response.
Gamma-delta T cells in the tissues around the mice's brains produced more IL-17 in response to the injection.
When the animals were treated with antibiotics, however, the amount of IL-17 was reduced, suggesting gamma-delta T cells could sense the presence of normal bacteria such as those that make up the gut microbiome, as well as invading bacterial species, and respond appropriately to regulate behavior.
"The immune system and the brain have most likely co-evolved," said first author and postdoctoral researcher Kalil Alves de Lima. "Selecting special molecules to protect us immunologically and behaviorally at the same time is a smart way to protect against infection. This is a good example of how cytokines, which basically evolved to fight against pathogens, also are acting on the brain and modulating behavior."
The researchers 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.
The findings are published Monday in Nature Immunology. ■