Image by Anita Impagliazzo, UVA Health System

A stunning discovery has been made at University of Virginia School of Medicine by the group of Jonathan Kipnis. In an article published on Nature this month, researchers have demonstrated that immune system can directly control brain areas which influence social behaviour.1

Since long time is known that immune system dysfunctions are associated with neurological and mental disorder. Despite the mechanisms of this process are mostly unknown, another study led by Prof Kipnis showed that meningeal immunity can support learning and memory, demonstrating a direct connection between peripheral immune cells and central nervous system.2

Differently, this new study links immune system activity and social behaviour; how did the authors demonstrate this association?

Firstly, researchers have used a three-chamber sociability assay. This assay evaluates whether a mouse prefers to spend more time investigating a novel mouse in the cage or an object. Differently from normal wild type mice, SCID mice (deficient in adaptive immunity) lacked any predilection for a mouse over an object.

Injecting immune cells in SCID mice, reversed the social dysfunction and mice started to interact together in the same way of the wild type counterpart.

After a meticulous molecular and behavioural analysis, researchers concluded that immune cells secrete a cytokine called IFN-γ, which in turn, regulates neuronal activity and favours social interaction.

What is astonishing is that IFN-γ is the master “weapon” used by our immune system to fight foreign pathogens. It was really unexpected that a molecule with such a role in immunity could also profoundly impact social behaviour.

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 sign of a pathology. And now, not only are we showing that they are closely interacting, but some of our behaviour traits might have evolved because of our immune response to pathogens,” said prof Kipnis, chair of UVA’s Department of Neuroscience, in an interview published on University of Virginia website. “It’s crazy, but maybe we are just multicellular battlefields for two ancient forces: pathogens and the immune system. Part of our personality may actually be dictated by the immune system.”3


So how did it come that a molecule involved in fighting pathogens can also directly control our neuronal activity?

A possible explanation is given by the leading author of the paper, Dr. Anthony J. Filiano:

“It’s extremely critical for an organism to be social for the survival of the species. It’s important for foraging, sexual reproduction, gathering, hunting. So the hypothesis is that when organisms come together, you have a higher propensity to spread infection. So you need to be social, but [in doing so] you have a higher chance of spreading pathogens. The idea is that interferon gamma, in evolution, has been used as a more efficient way to both boost social behaviour while boosting an anti-pathogen response.”3

Evolution always tries to optimize its processes. Life is really “energetically expensive”, thus generating molecules with multi-dimensional, pleiotropic effects, is extremely convenient from an evolutionary perspective. Authors also demonstrated that IFN-γ role in social behaviour is conserved across species: mice, rats, zebrafish and flies.There is no proof that this process holds true in humans, however, chances are really high.

Noteworthy, only one year ago the same research group broke the long-held belief that brain lacks lymphatic vessels4. And now, with this other breakthrough discovery, a new field of research stands in front of us in which immune system actively shapes our brain functions in both normal and pathological conditions.

Which are then the implications of this discovery?

A deep comprehension of these processes could advance our understanding of neural and psychic disorders and whether pathogen activities may impair and hijack these circuitries. Of course, complex diseases such as autism and schizophrenia are unlikely to be caused by a single molecules (e.g IFN-γ deficiency). Nevertheless, revealing that immune system – and probably pathogens – can profoundly impact our behaviours, encourage further studies that may open hitherto unexplored research avenues.

Davide Mangani



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