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The human gut is a remarkable study in contrasts. The intestinal lining is permeable enough to soak up the nutrients in food that pass through, yet it also serves as a barrier to thwart the harmful microbes it encounters.

The gut’s intricate and only partially understood defense strategy depends upon specialized immune cells that flag dangerous interlopers based on their antigens, the tiny identification tags that stud the surface of every microbial, plant, and animal cell. In some cases, however, overzealous immune cells can mistake foods, such as eggs, peanuts, and shellfish, as threats, triggering an allergic reaction characterized by inflammation.

“We have a very poor understanding of what is at the heart of food allergies,” says , the Helen L. and Martin S. Kimmel Professor of Molecular Immunology in the and a professor in the Department of at �����о��� Grossman School of Medicine. “It likely has to do with very complex interactions that go wrong involving cells of the immune system, cells of the nervous system, and the gut microbiota.”

In a new study published in the journal Nature, Dr. Littman and colleagues have revealed a previously unknown immune cell that could shed light on the basis of food allergies, as well as some gastrointestinal-based autoimmune diseases. Dendritic cells fight infection and disease by processing antigens and presenting them to other immune system cells to activate a response. The specialized dendritic cell discovered by the team may play a central role in activating anti-inflammatory cells to mute a full-throttle immune reaction—not only to specific foods, but also to microbes that might contribute to conditions such as inflammatory bowel disease.

“This latest research assembles a lot of different genetic models to give us the best definition to date of what this cell is,” Dr. Littman says. “I would predict that it’s going to be important in many of the genetic predispositions to inflammatory bowel disease; and various kinds of allergic reactions. It could also be involved in more general kinds of autoimmune diseases, such as type 1 diabetes.”

The has long explored how the immune system can ramp up or tamp down inflammatory reactions to perceived threats, and much of that action occurs in the gut. Infection-fighting white blood cells known as T cells abound there, including a specific kind called T helper 17 cells. These specialist soldiers assist in protecting and healing the intestinal barrier, though they can also provoke inflammation and have been linked to various autoimmune diseases.

Fortunately, each “go-getter” T cell has a corresponding “minder” T cell that keeps it in line. These regulatory T cells normally exist in a healthy equilibrium with their charges to curb harmful inflammation while still permitting necessary infection-fighting activity. “These regulatory T cells appear to be important for preventing susceptibility to allergic reactions in the gut,” Dr. Littman says. They also ward off overreactions to gut microbes that could contribute to disease.

Postdoctoral researcher Liuhui Fu, PhD, made the cell discovery while testing whether a mouse strain created in the lab more than a decade ago might have a defect causing an intolerance to some foods and microbes. It did, he found, resulting in highly inflammatory reactions to food and microbial antigens. “As it turns out, we had made a mutation that affected the ability of this newly described type of dendritic cell to program naive T cells to become regulatory T cells,” says Dr. Littman.

In other words, the new experiments demonstrated that the dendritic cell is essential for regulatory T cells to mature properly and enable the mice to tolerate certain food and gut microbes. Study co-author , assistant professor of medicine, identified the same cells in gut-adjacent lymph nodes from a human organ donor and showed that they corresponded to the mouse cells, suggesting that they could be therapeutic targets.

As with humans, some mouse gut microbes, including one called Helicobacter hepaticus, peacefully coexist with their host and may even provide some health benefits—unless, that is, immune dysfunction gives them an opening to cause disease. “As our study found, the dendritic cell that activates regulatory T cells is required both for food tolerance and for preventing bacteria like H. hepaticus from causing inflammation,” Dr. Littman says.

The finding suggests a potential therapeutic strategy. By ramping up the function of regulatory T cells trained on antigens, such as the ones specific to peanuts or the gluten in wheat (two of the most common food allergens), doctors might eventually be able to tamp down the excessive inflammation associated with an allergic reaction. The same general strategy could apply for subduing overreactions to microbes linked to other inflammatory diseases or for suppressing autoimmune conditions.

“It’s amazing how many questions have been raised by this discovery,” Dr. Littman says. “We have a lot of work to do, but we’re excited by the prospect that these unique cells could eventually become valuable therapeutic targets in multiple immune-related diseases.”