Our brains—and those of other social creatures—have circuitry that helps us navigate our interactions with other people. A new study suggests that these circuits might receive input from the immune system. Researchers led by Jonathan Kipnis of the University of Virginia report that a protein released by certain immune cells can influence social behavior in mice (Nature 2016, DOI: 10.1038/nature18626).
The findings, the scientists say, could someday help identify disrupted immune pathways involved in neurological diseases that affect social behavior, such as autism and schizophrenia.
In the study, Kipnis and his colleagues impaired the immune systems of mice so that the animals lacked mature T cells. The researchers tested the social behavior of these and normal mice by watching them in a three-chamber cage. One chamber contained an object the mice hadn’t seen before, and another had a new mouse. Normal mice, being social critters, prefer to hang out in the chamber with the other mouse, spending two to four times more time there than in the object chamber, says Anthony J. Filiano, the paper’s first author.
But the T cell-deficient mice showed no such preference—they explored both chambers equally. Mice with autismlike conditions also don’t have a preference in such experiments.
T cells aren’t present in healthy brains. So the scientists wondered how the cells could exert influence on neurons without directly interacting with them. They looked for a molecule released by the T cells that could signal to neurons.
Through bioinformatics analyses and further experiments, the team determined that the molecule was interferon-γ, a protein that helps fight off invading pathogens. The researchers could rescue social behavior in the T cell-deficient mice by injecting them with T cells. But if those T cells lacked the gene for interferon-γ, the mice remained antisocial.
Cornelius T. Gross, a neurobiologist at the European Molecular Biology Laboratory, Monterotondo, says the study presents exciting results for the field. But he points out that the mice receiving cells missing the interferon-γ gene show some preference for the mouse chamber, albeit not at a statistically significant level. This could mean another molecule besides interferon-γ may be involved, he says. Understanding which molecules are involved and where they are coming from is important, he says, “because showing that under noninjury conditions immune cells in the periphery can signal to and modulate the brain is indeed an important finding.”
Filiano says he and his colleagues want to study the mechanism further to understand how interferon-γ and similar molecules might regulate the activity of neurons.