It has been known for some time that immune cells and their signals can induce changes in our central nervous systems -- or CNS. But the link between the immune system and social behavior was unknown – until recently, thanks to new research out of Charlottesville. WMRA's Marguerite Gallorini reports.
Dr. Jonathan Kipnis is the Director of the Neuroscience Department and of the Center for Brain Immunology and Glia -- or BIG for short -- at the University of Virginia. He's been looking into the immune system connection with the central nervous system of mice for quite some time.
JONATHAN KIPNIS: When I was a graduate student, we started to be interested in the role of the immune system in response to injured CNS, and then from there the question was is the immune system playing a role in a normal CNS.
The CNS is the part of the nervous system mainly consisting of the brain and spinal cord.
KIPNIS: And so I started my own lab, with which we try to understand what are the exact molecules the cells produce to affect brain function.
After more than ten years, they finally discovered that a special disease-fighting molecule – called interferon gamma – was also responsible for social behavior. Anthony Filiano, a post-doctoral research fellow in Kipnis’s team, explains their recent study:
ANTHONY FILIANO: We found that interferon gamma has a pro-social role, and this was really unexpected to us and it was fascinating.
This was unexpected because the interferon gamma molecule is produced by immune cells, called T-cells, themselves produced by the lymphatic system – a crucial part of the immune system. So, since it is part of the lymphatic system, so far interferon gamma was only known for its anti-pathogen nature as Anthony mentioned – that means it was only known for responding to bacteria, viruses or parasites.
So to arrive at the discovery of this other social role, the UVa team studied flies, zebrafish, mice and rats; and they noticed that, when these animals were social, they activated the T-cells, releasing interferon gamma.
FILIANO: And we found that mice that are deficient for these immune cells – their brain goes haywire, it’s this… hyper connectivity in a part of the brain that’s important for social behavior. And so these mice have social deficits, and patients with autism, they also have this hyper connectivity.
But researchers still didn’t know exactly where that interferon gamma was located or coming from. That is when Antoine Louveau, a postdoctoral fellow in the Kipnis lab since 2014, came in:
KIPNIS: So when Antoine came to the lab, the question he was interested about was to understand where the immune cells that affect the brain are located. And that’s when he started to look into the meninges more closely.
The meninges are three membranes that envelope the CNS. Louveau explains his research process.
ANTOINE LOUVEAU: So we were able to analyze the meninges of old tissues. And when we did that, we realized that the immune cells were very localized at specific spots in the meninges, and they were along those major blood vessels called sinuses. And when we looked very closely at those vessels, we realized that they were lymphatic vessels.
So that is how they made two discoveries at once: Antoine demonstrated a direct link between the brain and the immune system, contrary to decades of thinking that the brain was “immune privileged,” that is to say lacking a direct connection to the immune system. And, they found that interferon gamma might affect social behavior. But why are the immune system and social behavior correlated in the first place?
FILIANO: So we created this hypothesis that when organisms become social, they would activate this interferon gamma response pathway to protect against the spread of pathogens while aggregating.
Indeed, many creatures need to interact for the survival of their species – but this same contact also makes the spread of diseases easier. That is why interferon gamma both makes them social, while protecting them from diseases that could come from such social interactions. That also explains why deficiencies in the immune system can lead to neurological disorders, such as depression, social anxiety, autism-spectrum disorder, or frontotemporal dementia.
FILIANO: And our pre-clinical study in mice show that interferon gamma is necessary for normal social function. We think that this suggests that perhaps interferon gamma signaling pathway might be a target for these diseases.
But this will require further research in the years to come.
FILIANO : Yeah so we…keep the clinical trials to the experts (laughs). It’s too early, these studies have been just done on mice, and… a lot more work needs to be done.
More needs to be done, especially in transitioning the research from mice to humans. But this first step in better understanding the link between social interaction and the immune system is very good news for the fight against neurological diseases stemming from immune deficiency.
For WMRA News, I'm Marguerite Gallorini.