How the brain spies on the intestines: with the help of newly acquired immune cells

Fighters against pathogens of the body can act as surveillance forces that transmit information from the intestines and fat deposits to the brain.

The immune cells of a special agent carry information about intestinal and adipose tissue deep into the brain. This observation system, found in mice, is crucial for the brain to control behavior such as the desire for food, researchers in Nature1 report today.

Such immune cells are known to fill the membranes that cover the brain, but newly identified cells have molecular traits that give them access to the core of the organ. Their function is formed by diet and microbiome; without them, even hungry mice eat slowly.

"It's very interesting to see it from an organ that was considered completely isolated from the immune system," says Michal Schwartz, a neuroimmunologist at the Weizmann Scientific Institute in Rehovot, Israel, who did not participate in the study.

Neighbor's clock

Almost every organ in the body has its own immune cells. Researchers have long believed that most of the "adaptive" immune cells of a healthy brain - those that target specific pathogens - are located in the brain membranes, three protective membranes that surround the brain.

Previous studies have hinted that adaptive immune cells called T cells can live inside the brain itself in stable conditions. But it was a difficult task to determine whether these cells really differ from cells in menipsychology, says Tomomi Yoshida, a neuroimmunologist at Yale University in New Haven, Connecticut, and co-author of the latest work. "They didn't really compare or contrast this element," she says.

To get a more definitive answer, Yoshida and her colleagues spent five years searching for T cells throughout the mouse brain. They found that T cells are concentrated in a hotspot in the Bfornical organ, a structure in the center of the brain that regulates a number of bodily processes, including eating and drinking. Then the scientists took tissue samples from the human subfornic organ, where they also found T-cells.

Both in the mouse brain and in the human brain, subfornic T-cells differed from those found in the brain. They produced more proteins that allowed them to seep into brain tissue and released more immunosignaling proteins known as cytokines under normal conditions.

Curiously, the researchers found that T-cells from the mouse brain were very similar to cells in animal fat deposits. To understand this similarity, they gave some mice a high-fat diet. As a result, these mice had more T cells in fat and brain tissues than mice that ate standard food, which indicates a link between fat mass and brain T-cell populations. After mice on the same diet fasted for 48 hours, the number of T cells in their brains increased and the amount of fat decreased, which suggests that food intake affects the number of T cells moving into the brain.

The connection between the cinetic and the brain

Then the researchers used antibiotics to deplete populations of intestinal microorganisms in some mice. The level of brain T cells in these animals has decreased, which may mean that the microbiome affects immune cell populations.

Finally, the researchers assessed the potential role of T cells living in the brain. Hungry mice, which were genetically constructed in the absence of T cells, took longer to find and consume food than control mice, which suggests that the brain T cells play a role in feeding behavior.

More work is needed to identify the mechanisms that allow brain T-cells to influence nutrition and other functions, says Emanuela Paschiuto, a neuroimmunologist at the Vlaams Institute of Biotechnology in Antwerp, Belgium. This will require the development of a completely new set of tools that record more than correlations, she adds. "It would be my experiment with desire."

Yoshida says that the team plans to unravel the role of brain T cells in more detail and find out how they interact with other cells.