Discovery could let doctors customize brain's immune response to diseases

April 11, 2018, University of Virginia
Jonathan Kipnis (from left), James C. Cronk and Christopher C. Overall, of the University of Virginia School of Medicine, have done what was thought impossible: find a way to get immune cells known as macrophages into the brain without the need for radiation. Credit: Josh Barney / UVA Health System

The University of Virginia neuroscience lab that discovered that the brain connects directly to the immune system now has found evidence that doctors could load up the brain with custom blends of immune cells to battle genetic disorders and neurodegenerative diseases such as Alzheimer's.

The UVA researchers were able to "engraft," or establish, immune cells known as inside the brains of lab mice without the need for radiation. Until now, many scientists had believed this impossible - the damaging radiation, they thought, would be vital to allow the to travel past the 's natural defenses.

"There are certain diseases where we already know that [the presence of macrophages] is clearly beneficial, but irradiation is a massive barrier clinically," said researcher James C. Cronk, PhD, of the UVA School of Medicine's Medical Scientist Training Program. "This supports the idea that you could do this and get these cells in the brain without having to irradiate, which is a huge step forward in terms of making it feasible."

Immune Cells and Neurological Diseases

The new research not only definitively establishes that macrophages can engraft into the brain without irradiation, but reveals what becomes of them once there. Previously, scientists had been uncertain if they would simply turn into another type of immune cell, known as microglia, that are abundant in the brain. The discovery that they remain a unique cell type suggests that doctors might be able to manipulate the mix to create custom immune responses to battle different diseases and disorders - and maybe even brain trauma.

"There are groups [of scientists] that have gone back and forth publishing papers on Alzheimer's or ALS debating whether during the normal process these cells are coming in and replacing not all but some of the microglia," Cronk said. "If you find out that engraftment is detrimental and we figure out what's bringing them in, you might block it. Or you might want to increase engraftment, depending on the condition."

Recognizing Immune Cells in the Brain

As part of their work, the researchers identified a "gene signature" to recognize and distinguish the enigmatic macrophages from other cell types, said researcher Christopher C. Overall, PhD, a computational biologist in UVA's Department of Neuroscience and its Center for Brain Immunology and Glia (BIG). "We identified a core set of genes for both the engrafting macrophages and microglia," he said. "Now, importantly, we can recognize engrafting macrophages as compared to microglia, and microglia really compared to anything."

Lead researcher Jonathan Kipnis, PhD, chairman of the Department of Neuroscience and director of the BIG Center, noted that the ability to detect the cells may eventually allow doctors to predict patients' risk of neurological disease. "It is very possible that these cells somehow get into the brain and then either predispose the brain to disorder or protect the brain from disorder," he said. "One day we may be able to say you probably will not have Parkinson's because you have these in that area."

Kipnis noted that the work represents an important interdisciplinary collaboration, bringing together scientists at both UVA's School of Medicine and UVA's School of Engineering and Applied Science. "The researchers in BIG had a fascinating image-analysis problem that no existing off-the-shelf software could solve," said Scott Acton, PhD, of the Engineering School's Department of Electrical and Computer Engineering. "If you think of microglia as resembling an octopus in shape, the BIG researchers needed to track the ends of the tentacles, the processes, and to measure their velocities and find their destination. We were able to provide an algorithm and a computer program that we can now make available to other researchers through this publication."

Cronk noted the collaboration has found answers to some major questions that have plagued brain researchers. "There is a very, very active area of research in terms of whether these macrophages are already present in neurodegenerative disease and whether they're beneficial or not," Cronk said. "We're establishing that yes, this is a unique cell type. ... The next step is, OK, what are they doing in the physiology? Can they be artificially put there, or removed, as a therapeutic strategy?"

The findings have been published online by the Journal of Experimental Medicine.

Explore further: Surprising contributor to Rett syndrome identified

More information: James C. Cronk et al, Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia, The Journal of Experimental Medicine (2018). DOI: 10.1084/jem.20180247

Related Stories

Surprising contributor to Rett syndrome identified

April 21, 2015
The immune system is designed to protect us from disease. But what if it was malfunctioning? Would it make a disease worse? That appears to be the case with Rett syndrome, a neurodevelopmental disorder, and possibly in other ...

Discovery reveals way to stop inflammation in Alzheimer's, arthritis, more

February 26, 2018
A new discovery about the immune system may allow doctors to treat harmful inflammation that damages the brain in neurodegenerative diseases such as Alzheimer's. It might also let doctors save patients from the potentially ...

Brain immune system is key to recovery from motor neuron degeneration

February 20, 2018
The selective demise of motor neurons is the hallmark of Lou Gehrig's disease, also known as amyotrophic lateral sclerosis (ALS). Yet neurologists have suspected there are other types of brain cells involved in the progression ...

Brain's immune cells linked to Alzheimer's, Parkinson's, schizophrenia

May 31, 2017
Scientists have, for the first time, characterized the molecular markers that make the brain's front lines of immune defense—cells called microglia—unique. In the process, they discovered further evidence that microglia ...

The brain's immune system may be key to new Alzheimer's treatments

March 7, 2018
Sanford Burnham Prebys Medical Research Institute (SBP) researchers have published two new studies in Neuron that describe how TREM2, a receptor found on immune cells in the brain, interacts with toxic amyloid beta proteins ...

Chinese scientists decipher origins of repopulated microglia in brain and retina

March 1, 2018
The regenerative capability of the central nervous system (CNS) is largely limited due to its intrinsic properties and external environment. Traditional thinking holds that once the brain is injured, it is impossible to repair ...

Recommended for you

Neural inflammation plays critical role in stress-induced depression

July 19, 2018
A group of Japanese researchers has discovered that neural inflammation caused by the innate immune system plays an unexpectedly important role in stress-induced depression. This insight could potentially lead to the development ...

Paralyzed mice with spinal cord injury made to walk again

July 19, 2018
Most people with spinal cord injury are paralyzed from the injury site down, even when the cord isn't completely severed. Why don't the spared portions of the spinal cord keep working? Researchers at Boston Children's Hospital ...

Understanding the neuroscience of binge drinking

July 19, 2018
A new study from researchers at Columbia University Irving Medical Center found that binge drinking impairs working memory in the adolescent brain. The study, in mice, explains why teenagers who binge drink are 15 times more ...

Scientists uncover the role of a protein in production and survival of myelin-forming cells

July 19, 2018
The nervous system is a complex organ that relies on a variety of biological players to ensure daily function of the human body. Myelin—a membrane produced by specialized glial cells—plays a critical role in protecting ...

Neurons can carry more than one signal at a time

July 18, 2018
Back in the early days of telecommunications, engineers devised a clever way to send multiple telephone calls through a single wire at the same time. Called time-division multiplexing, this technique rapidly switches between ...

Researchers solve mystery of how ALL enters the central nervous system

July 18, 2018
A deadly feature of acute lymphoblastic leukemia (ALL) is its invasion of the central nervous system.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.