Researchers at Washington University School of Medicine in St. Louis have identified previously unknown immune structures in the bone marrow of mouse skulls, potentially reshaping how scientists understand brain immunity.
The newly discovered lymph node-like formations, published in the journal “Nature,” responded to brain tumors before more distant lymph nodes located in the neck were able to do so.
When researchers disrupted the structures in mice with glioblastoma, an aggressive form of brain cancer, tumors grew faster and the animals died sooner than those with intact structures.
“The skull should no longer be viewed simply as a protective shell around the brain,” senior study author Jonathan Kipnis told reporters.
Kipnis added that the skull “contains specialized immune environments that appear capable of responding locally to changes within the brain,” marking a significant shift in scientific understanding.
The discovery carries an important caveat, as researchers have so far only demonstrated how these structures function in mice rather than in humans.
Kipnis was careful to note the limits of current human evidence: “We found similar immune cells in human skull marrow, suggesting that related structures may exist, but we have not yet demonstrated that they are organized or function in the same way as those in mice.”
For much of the 20th century, the brain was considered “immune privileged,” meaning it was thought to be largely isolated from the body’s conventional immune response due to the risk that inflammation could damage delicate brain tissue.
The blood-brain barrier reinforced this idea by tightly controlling what could pass from the bloodstream into brain tissue, but that understanding has changed dramatically in recent decades.
Kipnis’ lab helped drive that rethink in prior work, first identifying lymphatic vessels in the membranes surrounding the brain, and later showing tiny channels connecting those membranes to the skull’s bone marrow.
“The traditional concept of immune privilege has already changed substantially,” Kipnis said, adding that the new findings reveal specialized immune structures within the skull bone marrow sitting immediately adjacent to the brain.
In the experiments, researchers tracked proteins moving from mouse brains through microscopic skull channels into bone marrow, where they found organized clusters of B cells and T cells working together.
Study co-author Jang Hyun Park noted that “we have never seen such structures in healthy bone marrow before,” calling it an exciting discovery that points to the brain having its own dedicated immune defense system.
Marco Prinz, a neuroimmunologist at the University of Freiburg who was not involved in the study, described the finding as a “milestone,” saying that “nobody expected to find these lymph node-like structures in the skull.”
Prinz stressed, however, that researchers have yet to confirm that these hubs exist and function the same way in humans, calling that confirmation the field’s “major challenge” going forward.
“This would then indeed change how we view the central nervous system’s immune response in humans,” Prinz said, underscoring the broader significance of the research if replicated in human subjects.
When researchers stimulated the skull marrow of tumor-bearing mice with immune-boosting proteins, the treated animals rejected tumors more effectively and survived longer, raising the prospect of targeting skull bone marrow as a therapeutic avenue.
Any such treatment in humans remains a distant prospect, with Kipnis emphasizing the need to first confirm the structures’ organization, understand how they change across diseases, and determine how to manipulate them safely.
Kipnis said the potential implications could extend well beyond cancer: “If I had to bet, I would bet that these structures play a role in any brain disease that has an immune component to it.”
