Skull contains hidden immune hubs that protect brain health

Hubs of immune cells in the skull may help to defend our brain from ill health. A study into the brains of mice and human genetic data suggests that immune cells cluster in a particular area at the back of our skull. The discovery implies that targeting these hubs with drugs could bring new treatments for conditions where immune cells go rogue, such as brain cancer.

“It’s an important step forward in understanding the brain’s immune response,” says Vesa Kiviniemi at the University of Oulu in Finland, who wasn’t involved in the study. As well as being applicable for cancer, “it’s relevant for understanding things like infections, inflammatory brain diseases, multiple sclerosis [and] neurodegenerative diseases”, he says.

Immune cells called T- and B-cells are activated to act in the brain if they are presented with signs of threats, like fragments of tumours, in the lymphatic system. Now, Jonathan Kipnis at the University of Washington and his colleagues have uncovered another way these T- and B-cells are activated.

By imaging and analysing the skulls of mice, the team found that B- and T-cells cluster together with immune cells called antigen-presenting cells in immune hubs at the back of the skull. “These haven’t been described before,” says Kiviniemi. These hubs resemble lymph nodes, where antigen-presenting cells expose threats like tumour fragments to T- and B-cells.

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The team thinks these immune hubs are also in people. This is based on gene activity data collected from human skulls in prior studies, which suggest that T-cells were activated and helped activate B-cells in this part of the body. “It indicates the same is present in humans”, says Kiviniemi, although further studies analysing the skulls of cadavers are needed to confirm this.

To explore whether these hubs launch protective immune responses, the researchers injected cancer cells into the brains of mice. They then injected half the mice beneath the scalp with an experimental drug that disrupts the activation of B- and T-cells in the skull. This works by blocking a protein called CD40L on antigen-presenting cells, which helps them activate these immune cells. The remaining mice received saline injections.  

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The mice that received the drug went on to live for about 25 days, on average, after the tumour injection, whereas those in the placebo group lived 35 days. This suggests the immune hubs help to generate an anti-cancer immune response, says Kiviniemi.

In another experiment, a group of mice was given the same tumour injection, but this time, half received three drugs that enhanced the activation of B- and T-cells in their skull. These mice survived for about 10 days longer than others that got placebo injections.

If the same immune hubs are confirmed to exist in people, targeting them could bring new therapies for many brain-related conditions, says Kiviniemi. “We could figure out how to awaken and strengthen these [hubs],” he says.

Source: Newly discovered immune hubs in our skull may keep our brain healthy