Last year, we reported that researchers at the University of Virginia School of Medicine made the breakthrough discovery that the immune system and the brain are not isolated from one another as previously thought, but connected through a system of lymphatic vessels. The astonishing discovery of a "new" part of the human body opened the door to new ways of looking at immunity. Now, building on that research, the same team has made a potentially even more startling breakthrough: The immune system may play a key role in controlling and shaping social behavior. Their results were published recently in the journal Nature.

This surprising influence is the result of an age-old tussle between pathogens and immunity, they say. “History shows that [the] immune system affects social behavior, but why?” asks co-author Jonathan Kipnis, chairman of UVA’s department of neuroscience and lab leader for the project. “Things happen for a reason during evolution. Evolution is all about ancient forces: one is pathogens, and the other is the immune system that fights them; that’s how we acquired mitochondria and probably became multi-cellular organisms,” he tells mental_floss.

Anthony J. Filiano, lead author of the study and a postdoctoral fellow in Kipnis’ lab, says they set out to understand how “the immune system can have such a robust effect on the brain” without physically touching the brain. “There had to be some kind of soluble molecule or signal a T cell needed to produce to effect these distant neurons,” he says. They hypothesized that the immune cytokine interferon gamma [IG]—which is crucial to the immune system’s ability to fight pathogens like bacteria, viruses, and parasites—would be involved in social behavior, says Filiano.

Collaborating with the lab of immune system specialist Vladimir Litvack at the University of Massachusetts Medical School, they conducted a series of experiments on genetically modified mice. They compared signatures of cells that were treated with molecules produced by T cells and signatures from the brains of social rodents. The researchers found that IG works through inhibitory neurons that act as a kind of brake “to tone down the prefrontal cortex, which stops aberrant hyperactivity that has been shown to cause social deficits,” he adds.

When they blocked the IG molecule, the mice's prefrontal cortexes became hyperactive, and the mice became less social. When they restored the molecule function, the mice's brains returned to normal activity, and so did their behavior.

Filiano says they also looked back “across the evolutionary tree at rats, mice, fish, and flies” and found that when organisms were social, they were inducing an IG response. Even flies, which lack IG, “have the downstream target” for it, he says. They posit that "IG evolved to more efficiently control the spread of pathogens while organisms are being social. It has a dual role. We think the higher organisms have recycled these social genes into this anti-pathogen gene,” Filiano says.

He and Kipnis are excited about the implications for treating neurological disorders and behavioral disorders. Filiano says, “It’s fun to speculate that perhaps small changes in immunity can affect our day-to-day behaviors.”

Listen to the researchers discuss more details their findings in the video below.