Food allergies can be severe and sometimes life-threatening. Yet for most people, the immune system accepts the foods they eat every day without any trouble.
A new study from researchers at Stanford University helps explain why.
The research, published in Science Immunology, suggests that the body doesn’t simply ignore food proteins. Instead, specialized immune cells actively recognize certain molecular signals in foods and use them to teach the immune system that those foods are safe.
“We know a lot about what the immune system sees and does if a patient has an allergy, but we know very little about what happens when things go right,” said Elizabeth “Beth” Sattely, associate professor of chemical engineering at Stanford University and senior author of the study.
For years, scientists assumed that food tolerance worked mainly because the immune system overlooked harmless foods. But the new research supports a different idea: tolerance is an active biological process.
Certain immune cells in the intestines constantly sample the foods we eat. These cells, known as regulatory T cells, or Tregs, act as the immune system’s “peacekeepers.” When they encounter specific fragments of food proteins, they signal the immune system not to launch an inflammatory response.
In the new study, researchers identified several of these molecular fragments, known as epitopes, that appear to encourage this calming immune reaction.
The team examined diets used in laboratory mouse studies that included ingredients common in human foods such as corn, wheat and soy. They found that regulatory T cells responded strongly to a limited set of protein fragments within those foods.
“What really surprised me was how focused the mechanism is,” said co-author Ryan Kong, a Stanford graduate student. “In the case of corn, the Treg cells zero in on a single epitope that is part of a larger molecule, zein, a protein in the fleshy interior of the corn kernel.”
That finding suggests the immune system may rely on a relatively small number of molecular cues to learn which foods are safe.
The researchers say the discovery could help explain why some people develop food allergies while most do not. If the immune system fails to recognize or respond to these tolerance-promoting signals, it may be more likely to treat a food as a threat.
The work also highlights the role of the gut environment in shaping immune responses to food. The researchers found that both the structure of food proteins and the composition of intestinal microbes can influence whether these tolerance signals are generated.
“One of the most exciting findings is that the development of the zein-specific T cells depends on the format of the protein in the food and the intestinal microbial community,” said co-author Jamie Blum, now a faculty researcher at the Salk Institute.
Although the research was conducted in mice, the team believes the same biological principles likely operate in humans.
Understanding those mechanisms could eventually lead to new strategies for preventing or treating food allergies. Scientists might be able to design therapies that encourage regulatory T cells to promote tolerance instead of triggering allergic reactions.
Researchers are also exploring whether these tolerance-promoting protein fragments could be used to guide early immune training during childhood.
“We might be able to treat a patient who currently has a food allergy and induce these regulatory T cells that would allow them to overcome their allergy,” Sattely said. “Or, we could design early-stage, childhood exposures that would guide allergy-prone patients toward tolerance before allergies develop.”
For now, the study provides a clearer picture of how the immune system interacts with food and why most people can safely eat a wide range of foods without triggering harmful immune responses.
Rather than simply ignoring food, the body appears to actively learn that certain foods are safe.
The research was supported by the Howard Hughes Medical Institute, the National Science Foundation, the National Institutes of Health, the Rosenfield and Glassman Foundation and the ONO Pharma Foundation.