For decades, scientists have generally viewed the brain's immune system as largely separate from the immune defenses operating throughout the rest of the body. The brain has its own specialized immune cells, along with the blood-brain barrier, which restricts many substances and cells from entering brain tissue. New research from Stanford is challenging that picture.
Scientists found that large numbers of immune cells from elsewhere in the body enter the human brain as people age. The discovery could reshape scientists' understanding of brain aging and may eventually create new possibilities for treating neurological diseases. The work, supported in part by the Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, was published recently in the journal Nature.
"We usually think of the brain as a closed system," said Julia Belk, a postdoctoral scholar in pathology at Stanford Medicine and first author on the new study. "What we found is that actually a lot of immune cells enter the human brain during aging." Belk's interest in neuroscience began while she was a graduate student in the Department of Computer Science at Stanford Humanities and Sciences. During that time, she also trained through Sarafan ChEM-H's Chemistry/Biology Interface Predoctoral Training Program.
She has described that experience as important in shaping an interdisciplinary approach that combines basic science, computer science, and medicine. That training eventually led to a collaboration with Siddhartha Jaiswal, a senior author of the new study, an associate professor of pathology at Stanford Medicine, and a member of the Institute for Stem Cell Biology and Regenerative Medicine. In earlier work, the researchers examined genetic information from thousands of people, including some who had been followed for decades.
The team showed that people carrying certain clones of immune cells produced by mutated blood stem cells were much less likely to develop Alzheimer's. That result raised the possibility that these unusual immune cells might somehow be interacting with the brain. The researchers later found evidence that some of the mutant cells could enter the brain itself.
The mutations involved are associated with clonal hematopoiesis of indeterminate potential, a condition found in only a minority of people. Even so, the discovery led the team to ask a broader question: Could immune cells from the blood routinely enter the brains of people as they grow older? "Unlike most immune cells, which are continuously replenished by blood stem cells from the bone marrow, immune cells in the brain were presumed to renew themselves throughout the lifespan without contribution from outside the brain," said Jaiswal.
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