Discovery Could Let Doctors Customize Brain’s Immune Response to Diseases

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 macrophages 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 immune cells to travel past the brain’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 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 disease 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, a computational biologist in UVA’s Department of Neuroscience and its Center for Brain Immunology and Glia. “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, chair of the Department of Neuroscience and director of the Center for Brain Immunology and Glia, noted that the ability to detect macrophages may eventually allow doctors to predict patients’ risk of neurological disease.

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