Immune System Controls Social Behavior, Study Finds

Drs. Anthony J. Filiano (L), and Jonathan Kipnis (R) of the UVA  Department of Neuroscience recently made a startling discovery about the immune system. (Photo courtesy of University of Virginia Medical School)

Your immune system protects you from disease. New research finds that it may even control your behavior. A study published on July 13 in the journal Nature may point the way toward future treatments for neurological conditions.

The immune system connects to the brain in ways that scientists are only beginning to understand.  Since the 1930s, researchers have noted a strong correlation between neurological dysfunction—such as schizophrenia, autism, and Alzheimer’s disease—and symptoms of immune system dysfunction, such as autoimmune disease, and gastrointestinal problems. But how these pieces fit together has remained a mystery.

For decades, the immune system was thought to have no direct connection to the brain because it had no connection to the lymphatic system (the network that carries immune cells throughout the rest of the body). But last year, researchers from the University of Virginia (UVA) School of Medicine found evidence of meningeal vessels, which linked the brain to the lymphatic system. This textbook-changing discovery opened up a whole new avenue of research to help explain the brain-immune system connection.

Under the direction of Dr. Jonathan Kipnis, chairman of UVA’s Department of Neuroscience, the team’s latest discovery finds that restricting a single type of immune molecule (interferon gamma) causes parts of a mouse’s brain to become hyperactive, leading to socially abnormal behavior.

Mice are social creatures that typically seek the company of fellow mice, but take away their interferon gamma and they suddenly turn into loners. When the molecule was restored, brain function and social habits returned to normal.

If removing just one immune molecule can significantly affect social behavior, it suggests that our immunity may play a larger role in our lives than we realize.

“It’s crazy, but maybe we are just multi-cellular battlefields for two ancient forces: pathogens and the immune system. Part of our personality may actually be dictated by the immune system,” said Kipnis in a statement.

Easier to Target

This study gives us our first glimpse into how our immune systems steer our decisions, and it may also lead to new treatment options for people suffering from neurological conditions.

Previous examinations of neurological disease focused primarily on brain cells. But according to Dr. Anthony J. Filiano, a postdoctoral fellow in the Kipnis lab and lead author of the study, considering a neurological disease from the perspective of the immune system may actually be a more practical approach.

“A lot of the preclinical studies have targeted synapses in the brain, and all of these therapies have failed,” Filiano said. “The immune system, just because of our access to it, is a lot easier to target.”

The immune system may be a more accessible route, but picking apart its biological mechanisms still require a lot of strategic thinking.

“These experiments are expensive and there are over 100 types of immune molecules that can potentially affect neurons in the brain, so it’s not feasible to just go in and investigate one at a time,” Filiano said. “We need to be smart about it and make appropriate predictions and well-designed experiments.”

Mapping a Road to Treatment

Filiano’s findings suggest that we’re at the dawn of a new understanding in regard to immunity, the biology of social behavior, and even free will. But it’s still not clear whether it will ultimately mean anything for treating human disease. Do the social deficits that often accompany autism and schizophrenia actually stem from a malfunctioning immune system similar to the mice in the study? And if so, how does that translate into a treatment?  

To help answer to these questions, the UVA research team is collaborating with National Institutes of Health researchers who are studying patients who have mutations in their neural pathways (a characteristic of disorders such as schizophrenia and autism). Filiano says that if biologists can find the pathways that are involved in human social behavior, they may be able isolate some new therapeutic targets.

Hopefully, we can map out how different molecules affect different neural circuits, and affect different behaviors, and really see the communication between the immune system and the brain,” he said.

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