Stanford University researchers announced on Mar. 11 that they have uncovered how the immune system actively builds tolerance to foods, a discovery that could lead to new treatments for food allergies. The findings were published in the journal Science Immunology.
The research is significant because it addresses why most people can safely eat foods that cause severe allergic reactions in others. Understanding this process may help scientists develop therapies to prevent or reverse dangerous food allergies.
Elizabeth "Beth" Sattely, associate professor of chemical engineering at Stanford and senior author of the study, said, "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." Sattely and her team found that oral tolerance involves regulatory T cells (Tregs) recognizing specific proteins in common foods such as corn, soy, and wheat. These Tregs act as peacekeepers by calming the immune response when they detect these proteins, preventing allergic reactions.
The study identified particular fragments of dietary proteins—called epitopes—that stimulate a regulatory response from Treg cells rather than triggering inflammation. Jamie Blum, former postdoctoral scholar in Sattely's lab and now leading her own lab at The Salk Institute for Biological Studies, explained that development of zein-specific T cells depends on both the protein format in food and the intestinal microbial community. "We are now working to determine the exact biological mechanisms involved," Blum said.
Ryan Kong, a Stanford graduate student and co-first author of the study, noted how targeted this mechanism is: "What really surprised me was how focused the mechanism is. In the case of corn, the Treg cells zero in on a single epitope that is part of a larger molecule, zein... Considering the enormous number of potential intestinal antigens, it was striking to see such a targeted response." Kong added that understanding why certain peptides are selected could help reprogram immune responses to prevent or treat allergies.
Looking ahead, Sattely envisions creating molecular maps of tolerance-biased epitopes to guide new therapies or even preventative vaccines for those at high risk for food allergies. She said future research will focus on plant chemistry and engineering food proteins to test their effects on immunity: "For now, we've learned that tolerance is defined as more than the mere absence of allergy. It is a specific, peptide-guided immune training program that we can someday harness to help people eat without fear."
