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Maddy Chapman
Original story from Washington University School of Medicine (MO, USA).
A novel ‘immune organ’ inside the skull directs brain defense and may offer a new way to fight brain cancer and neurodegenerative disease.
Researchers at Washington University School of Medicine in St. Louis (MO, USA) have discovered lymph node-like structures in the skull bone marrow of mice for the first time and demonstrated that they act as rapid first responders against brain cancer before distant lymph nodes get the signal that abnormal cells are present. The researchers also found evidence of similar immune cells in human skull bone marrow.
For decades, scientists assumed that the brain and the immune system did not communicate. The new study reveals that the brain not only communicates with the immune system but also has positioned immune ‘security stations’ nearby, closer than other organs do.
The study, published Aug. 19 in Nature, is the first to find such immune hubs in bone.
“This study reveals that the skull bone marrow is far more than just a structural framework – it harbors previously unrecognized hubs for brain-specific immune responses,” explained senior author Jonathan Kipnis. “Uncovering this localized immune niche changes how we view neuroimmune interactions and opens exciting new avenues for treating brain tumors and other neurological diseases.”
The brain’s dedicated first responder
Kipnis’ lab challenged the once widely accepted idea that the brain is shielded from the immune system when they discovered lymphatic vessels running through the dura mater, the outer tissue layer enveloping the brain underneath the skull. More recently, his team identified tiny physical channels bridging the skull, dura and brain tissue, revealing a direct conduit for immune cells and cellular waste to move between the brain and local skull bone marrow.
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In the new study in mice, they tracked the movement of proteins from the brain through the channels directly into the skull’s bone marrow, where they uncovered immune system structures typically found in the lymph nodes. These act as the immune system’s training hub where T follicular helper cells, a kind of immune cell, assist other immune cells called B cells in creating large amounts of powerful antibodies that help fight disease and infection.
“We have never seen such structures in healthy bone marrow before,” exclaimed Jang Hyun Park, the study’s first author. “It is an exciting discovery that points out that a complex brain requires its own specialized immune structures to defend it.”
How can the skull’s immune system combat cancer?
To test whether these nearby hubs actively protect against brain disease, the team used a model of glioblastoma, an aggressive form of brain cancer. They found that in mice with brain cancer, disrupting the skull immune hubs with a drug caused tumors to grow faster than in mice with intact hubs. Impairing their function caused a drop in survival, showing that the brain actively relies on these local centers for defense against cancer.
The researchers also developed a targeted therapy designed to supercharge antibody production inside the skull marrow. By delivering a mixture of three immune-boosting proteins using a gel applied directly under the scalp, the researchers prompted a wave of tumor-fighting immune responses to attack the cancer. These responses, the research found, occurred first in the immune hubs in the skull bone marrow, then later in nearby lymph nodes outside the skull. Mice given the gel experienced better tumor rejection and lived longer compared with control mice.
“The finding fundamentally changes our current understanding of neuroimmunology,” continued Kipnis. “Knowing that the brain relies on first responders in the surrounding skull for defense has the potential to change how we think about developing therapies for many neurological conditions, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, long COVID and many others that have an immune component to them. Such therapies could access these immune hubs directly through the skull, without major peripheral side effects.”
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