Immune system signaling can directly affect social behavior

Using a systems-biology approach, scientists at the University of Massachusetts Medical School made a startling discovery that immune system signaling can directly affect, and even change, social behavior in mice and other model animals. Published in Nature, these findings could have great implications for neurological diseases such as autism-spectrum disorders and schizophrenia.

"Using this approach, we predicated an unexpected role for interferon gamma (IFN-γ), an important cytokine secreted by T lymphocytes, in promoting social brain functions," said Vladimir Litvak, PhD, assistant professor of microbiology & physiological systems at UMMS. "Our findings contribute to a deeper understanding of social dysfunction in neurological disorders, such as autism and schizophrenia, and may open new avenues for therapeutic approaches."

Dr. Litvak and Yang Xu, a PhD student in the Graduate School of Biomedical Sciences at UMMS, developed and employed a novel systems-biology approach to investigate the complex dialogue between immune signaling and brain function in health and disease. Using this approach, Xu defined canonical immune signaling signatures and analyzed for their presence in thousands of publicly available brain transcriptome data-sets. These studies uncovered a hidden connection between T-cell mediated immune signaling and social brain function.

Litvak and colleagues found that various organisms, including rodents, fish and flies, elevate IFN-γ signaling in social contexts. These findings suggest that the IFN-γ signaling pathway could mediate a co-evolutionary link between social behavior and an efficient anti-pathogen response that might be critical for herd immunity.

This work was done in collaboration with researchers at the University of Virginia. Jonathan Kipnis, PhD, chair of neuroscience at the UVA School of Medicine showed that blocking IFN-γ in mice made mouse brains become hyperactive and caused atypical social behavior. Restoring of IFN-γ-signaling in the brain normalized brain activity and social behavior. "The brain and the adaptive immune system were thought to be isolated from each other, and any immune activity in the brain was perceived as a sign of pathology. And now, not only are we showing that they are closely interacting, but some of our behavior traits might have evolved because of our immune response to pathogens," explained Dr. Kipnis.

The researchers note that a malfunctioning immune system may be responsible for "social deficits in numerous neurological and psychiatric disorders." But exactly what this might mean for autism and other specific conditions requires further investigation.

"For the first time we have a platform capable of systematically investigating the complex connections between immune signaling and various brain functions," Litvak said. "I believe that anybody can use our technology as a template to investigate the involvement of various immune components in different brain dysfunctions."