UVA researchers discover immune cells call the shots

Anthony Filiano led the study that suggests immune cells control social behavior, which could impact schizophrenia and autism spectrum disorders.
Anita Impagliazzo/UVA Health Anthony Filiano led the study that suggests immune cells control social behavior, which could impact schizophrenia and autism spectrum disorders. Anita Impagliazzo/UVA Health

Groundbreaking research has emerged from UVA researchers showing that immune cells control social behavior. Last year, the same lab debunked a long-held scientific belief that the brain lacked a connection with the immune system, which will require medical textbooks to be rewritten.

The researchers, led by Jonathan Kipnis, chairman of the department of neuroscience in UVA’s Medical School, are a part of the Kipnis lab, a group that believes risky and even crazy experiments are what move science forward, according to the lab’s website.

Initial experimentation found that immune-deficient mice have social deficits, which led the researchers to examine the brain and map out which neural circuits may be affected.

Using a procedure known as resting-state functional MRI, the researchers evaluated interactions that occurred within the brain when it is not performing an explicit task. Through this method, they discovered regions in the prefrontal cortex (PFC) that were interacting irregularly with one another.

This discovery steered the researchers to concentrate on the PFC.  Located in the front part of the brain, the PFC is believed to have an integral influence in personality expression, social behavior and decision-making.

The UVA researchers discovered that the immune system not only directly affects a creature’s social behavior, but also controls it. The prefrontal cortex is critical in determining social behavior and, in mice, overactivating the PFC results in social discord.

The study shows how an immune cell-derived molecule, interferon-gamma, acts as a rheostat, an instrument used to control electrical current that limits hyper-connectivity in the PFC. The release of these interferon-gamma cytokines (IFN-g) envelopes the lab’s future work.

“Our hypothesis is that through the release of IFN-g, the immune system can influence behaviors, such as sociability, by directly modulating neural circuits,” says Anthony Filiano, the lead author of the study.

Because neurons and synapses have been difficult to target therapeutically, the immune system may offer a new avenue for intervention.

“Our finding demonstrates, at least in mice, that we can manipulate the immune system from the periphery and influence the inner workings of the brain,” Filiano says.

Currently, the preclinical study is using mice; however, this discovery could have significant implications regarding neurological diseases such as schizophrenia and autism spectrum disorders.

“Given the mounting evidence that immune dysfunction is present in most neurological disorders, and targeting the immune system is historically easier than neurons, neuro-immune interactions are a very attractive new therapeutic target,” Filiano says.—Melissa Angell

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