Article Summary: Guardians of the Brain – The brain’s borders teem with an army of immune cells that monitor and protect it.

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The blood-brain barrier functions as an extra protective layer to protect the brain from any potentially damaging agents in the rest of the body. It is such a strong barrier, though, that most researchers thought it separated the brain from the body’s immune system as well. But, as Diana Kwon reports in Nature, new work suggests that this separation is not as absolute as once thought. Immune cells are found in the membranes surrounding the brain, and they can send molecular signals into the nerve cells within.

Take-Aways

• Many types of immune cells cannot cross the blood-brain barrier, but others patrol the borders and can send in signaling molecules.
• As in the rest of the body, immune cells in the brain play vital roles in both healthy and pathological states.
• Nerve cells and immune cells constantly communicate back and forth, each influencing the others’ behavior.

Summary

Many types of immune cells cannot cross the blood-brain barrier, but others patrol the borders and can send in signaling molecules.

The blood-brain barrier protects brains from pathogens and any other potentially harmful agents that aren’t supposed to be there. It also separates the brain from much of the mundane goings-on in the rest of the body – including, it had long been assumed, the immune system. But research conducted over the past 10 years or so overturns that assumption, indicating that immune cells surround the brain and communicate with neurons.

“The brain is the body’s sovereign, and receives protection in keeping with its high status.”

The brain has its own special immune cells, called microglia. Most researchers thought that this was the extent of the interaction between the brain and the immune system. But in 1999, Michal Schwartz, a neuroimmunologist at the Weizmann Institute of Science in Israel, reported that macrophages and T cells helped heal an acute injury in the central nervous system in rats. Since then, immune cells like these have been found in the meninges, the membranes that surround the brain and spinal cord. And in 2021, Jonathan Kipnis, a neuroimmunologist at Washington University in St. Louis, discovered that the bone marrow of the skull can supply immune cells to the brain in mice in response to an injury or pathogen.

As in the rest of the body, immune cells in the brain play vital roles in both healthy and pathological states.

It’s not yet clear if the immune cells in the brain are a net boon or bane. They could be protective, and clear away harmful structures like the amyloid plaques that accrue in Alzheimer’s disease. But they can also promote inflammation and cell death.

“A large body of evidence now shows that the brain and the immune system are tightly intertwined.”

Microglia, the brain-specific immune cells, certainly play a vital role in normal neurological development. They prune neuronal connections, but disruptions in this pruning process can lead to abnormal behavior.

Nerve cells and immune cells constantly communicate back and forth, each influencing the others’ behavior.

So far it seems that the immune cells in the meninges stay at the border of the brain and do not go in. But they send in signaling molecules called cytokines. Studies in animal models demonstrated that changing these cytokine signals can affect memory, learning and social behaviors.

“Although these insights are tantalizing, much of the work on how immune cells, especially those in the borders, operate in the brain is still in its infancy.”

And despite the separation of the blood-brain barrier, neurons can send signals to the immune system in the periphery. Asya Rolls, a neuroimmunologist at Technion-Israel Institute of Technology, showed that activating neurons in a brain region involved in motivation and the brain’s reward system boosted the immune response and even slowed tumor growth in mice. Her lab later showed, again in mice, that neurons in a brain region that helps process emotions are active during gut inflammation; artificially activating these neurons spurs the same inflammation. The brain stores and retrieves this immune response as if it were a memory. She noted that this could help explain how psychological states can impact the immune response, suggesting a mechanism for psychosomatic disorders – and how to treat them.

About the Author

Diana Kwon is a freelance science journalist based in Berlin. She covers the life sciences, health and academic life. Her work has appeared in publications such as Scientific American, The Scientist, Nature and Quanta.