Yale Researchers Identify Gut-Linked Immune Cells in the Brain

Yale School of Medicine researchers have discovered, for the first time, specialized immune cells in the brains of mice and humans which may facilitate communication between the gut and brain.

In a study published May 28 in Nature, a team led by Tomomi Yoshida, PhD candidate in the Department of Immunobiology, found never-before-seen CD4 T cells in healthy brains. The cells shared more characteristics with immune cells that reside in the gut than those typically found in tissues surrounding the brain and were most densely concentrated in a region of the brain known to regulate thirst and hunger.

We've known that there's a gut-brain connection, but how it actually works has been a little bit fuzzy. Here we've discovered a cellular communication system that transmits information about the gut, including food intake."

Andrew Wang, MD, PhD, associate professor of Internal Medicine (Rheumatology, Allergy and Immunology) and of Immunobiology and co-senior author of the study

In animal models, changes in gut contents impacted the presence and number of T cells in the brain. Researchers say the findings shed new light on how the gut communicates with the brain about when it's full and what has been eaten.

"We essentially showed that depending on what you put into the body, you send different cells to the brain," said David Hafler, MD, professor of Immunobiology and of Neurology and chair of the Department of Neurology, who was co-senior author of the study. "So what you eat changes the brain's composition."

The Yale team says future work will focus on how these T cells move from the gut to the brain -- and what role they may play in conditions such as multiple sclerosis, autoimmunity, and Parkinson's disease.

"Especially as we have national conversations about ultra-processed foods and the impact of what we put into our bodies," Hafler said, "learning more about how our diet impacts the development of our brains will improve health outcomes and save lives."