Immune system lends the brain a hand


Study adds fuel to growing evidence that the immune system does more than fight disease. Paul Biegler reports.


It turns out that a pro-inflammatory cytokine boosts memory when kept in the “Goldilocks zone”.

Valerie Altounian

Researchers have discovered that the immune system helps out the brain, in the absence of any disease, by making a chemical messenger that boosts memory.

The study was in mice, but senior author Bruno Silva-Santos, from the University of Lisbon, Portugal, says the finding could lead to dietary recommendations to improve memory in people.

The study is part of a rising tide of research upending the traditional view that the immune system exists only to fight infection and tumours.

The authors point out that disease is relatively rare, and so maintaining a complex system of immunity would impose a big cost if busting microbes and cancer were the only benefit.

Already, they say, immunity is known to have non-disease roles in temperature control and bone repair. But to accept that the immune system could be a major player in the everyday workings of the brain, another shibboleth in medicine must fall by the wayside.

“The brain was seen as an immune privileged organ, meaning that it would be completely shielded by the blood brain barrier and completely hermetic to the peripheral immune system,” explains senior author Julie Ribot, in a linked video.

Recently, says Ribot, it has been found that lymphatic vessels, which transport infection-fighting white blood cells, are present in the lining of the brain, called the meninges.

“This is really important,” says Ribot, “because it suggests that actually the brain and the immune system do constantly communicate, even when we are not sick.”

The presence of a workaday brain-immune relationship is born out in recent studies showing white cells, called T lymphocytes, are key for spatial learning and social behaviour.

But the team had a hunch there was an even broader connection.

They believed a type of lymphocyte known as a gamma delta T cell, which is resident in the meninges, could be crucial for memory. So they devised some clever experiments in mice that were specifically engineered to lack gamma delta cells.

When they put those mice to the test in a maze, the critters’ short-term memory – the bit that helps you remember what you had for lunch today, but not last week – was shot.

The finding was pleasingly consistent with the researchers’ theory, but how those gamma delta cells were helping memory came as a curve ball.

“We thought gamma delta cells would be pro-cognitive,” says Silva-Santos.

“What was very surprising was that … the molecule they secrete to endow cognition is actually IL-17,” he says.

Surprising, explains Silva-Santos, because IL-17 (interleukin-17) is what’s known as a “pro-inflammatory cytokine”. It’s something of a bad boy, known to cause inflammation and contribute to disease, notably multiple sclerosis.

But IL-17, the researchers found, is also a trigger for brain derived neurotrophic factor, (BDNF) a prolific neuron fertiliser that enhances signalling between brain cells in the hippocampus, a major memory centre.

The team now thinks IL-17 has to be kept in the Goldilocks zone – too much and you get inflammation and disease, too little and memory suffers.

Silva-Santos has some ideas on how we might one day get IL-17 just right.

“What will be important to know is what are the factors that regulate these basal levels of IL-17... so that we can, for instance through diet, because we have realised that vitamins can regulate this process ... have enough IL-17 in our brains, in our meninges, to guarantee proper short term learning,” he says.

The study appears in the journal Science Immunology.

Contribs paulbiegler 2.jpg?ixlib=rails 2.1
Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
  1. https://www.jimmunol.org/content/198/7/2681.abstract
  2. https://www.nature.com/articles/nature18626
  3. https://www.ncbi.nlm.nih.gov/pubmed/26953244
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/
  5. https://immunology.sciencemag.org/
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