Researchers have discovered immune centers resembling lymph nodes within the skull’s bone marrow; these appear to act as rapid-response hubs for the brain.
For decades, it was believed that the brain functioned largely independently of the immune system. However, researchers at Washington University School of Medicine in St. Louis (WashU Medicine) discovered lymph node-like structures in the skull bone marrow of mice that respond rapidly to brain cancer—doing so before more distant lymph nodes receive signals about the presence of abnormal cells. They also found evidence of similar immune cells in human skull bone marrow.
These findings add to a growing body of evidence that the brain interacts directly with the immune system and suggest that specialized immune centers are located unusually close to the organ they help protect.
The study, published in the journal Nature, is the first to identify such immune centers within bone tissue.
“This study shows that skull bone marrow is much more than just a structural framework; it houses previously unknown centers for brain-specific immune responses,” said lead author Professor Jonathan Kipnis of WashU Medicine. “Uncovering this localized immune niche changes our understanding of neuro-immune interactions and opens up exciting new possibilities for treating brain tumors and other neurological diseases.”
Kipnis’s laboratory previously overturned the long-held belief that the brain is isolated from the immune system by discovering lymphatic vessels in the dura mater—the outer tissue layer surrounding the brain beneath the skull. Researchers recently identified tiny physical channels connecting the skull, the dura mater, and brain tissue, creating a direct pathway for immune cells and cellular waste to travel between the brain and the adjacent skull bone marrow.
In recent experiments involving mice, researchers tracked the movement of proteins from the brain through these channels into the skull bone marrow. There, they discovered immune structures typically associated with lymph nodes. Such structures act as training centers where T follicular helper cells assist B cells in producing large quantities of antibodies that help defend against infections and diseases.
“We had never seen structures like this in healthy bone marrow before,” said study co-author Chan Hyun Park. “This is an exciting discovery, suggesting that the complex brain requires its own specialized immune structures for protection.”
To determine whether these immune centers in the skull actually contribute to protection against brain diseases, the researchers turned to a mouse model of glioblastoma—an aggressive form of brain cancer. When they disrupted the function of the skull’s immune centers using a drug, tumors grew faster than in mice whose centers remained intact. Disrupting these structures also reduced survival rates, indicating that these nearby immune centers help protect the brain against cancer.
“This discovery fundamentally changes our current understanding of neuroimmunology. Knowing that the brain relies on precursor cells in the surrounding skull for protection could potentially reshape how we approach developing treatments for many neurological conditions, including Alzheimer’s disease,” the authors note. The researchers then tested whether boosting immune activity in the skull bone marrow could improve the anti-cancer response. They applied a gel containing three immune-boosting proteins directly beneath the scalp, stimulating increased antibody production in the skull bone marrow. Tumor-fighting immune responses appeared first in the skull’s immune centers and only later in nearby lymph nodes outside the skull. Treated mice rejected tumors more effectively and lived longer than control mice.
“This discovery fundamentally changes our current understanding of neuroimmunology,” said Kipnis. “Knowing that the brain relies on immune defense centers…” in the surrounding skull could transform our approach to developing treatments for many neurological conditions—including Alzheimer’s disease, Parkinson’s disease, schizophrenia, long COVID, and numerous others with an immune component. Such therapies could target these immune hubs directly through the skull, avoiding serious side effects affecting peripheral organs.
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