Typically, the intestinal immune system is adept at distinguishing beneficial substances from harmful ones, allowing a variety of foods while neutralizing pathogenic invaders. However, for about 30 million Americans suffering from food allergies — including 4 million children — immune cells incorrectly perceive food as a danger, triggering reactions that could be life-threatening.
Recently, scientists at Washington University School of Medicine in St. Louis discovered, in mice, that vital immune cells in the intestine inhibit unnecessary assaults against benign food allergens. In the absence of these cells, mice exhibited gut inflammation and displayed allergic reactions to food.
Their findings were published online on April 3 in Cell and will be available in print on May 15.
“We are observing a swift worldwide rise in food allergies that profoundly affects quality of life,” stated Marco Colonna, MD, Robert Rock Belliveau, MD, Professor of Pathology at WashU Medicine. “The scarcity of treatments to prevent and manage food allergies complicates this escalating public health concern. Now that we have identified the entities that promote tolerance to food allergens, we can create innovative approaches to target them therapeutically, possibly to avert or remedy food allergies.”
The immune system confronts prevalent food allergens — such as peanuts, tree nuts, milk, eggs, and shellfish — without instigating a self-destructive immune attack in a mechanism known as tolerance. A breakdown in tolerance to food incites an allergic response with symptoms that range from mild hives and itching to severe, potentially fatal allergic reactions that can lead to throat swelling and breathing difficulties, necessitating immediate intervention. As part of the current research, the scientists focused on the factors preventing such responses, which may assist in developing preventive therapies for food allergies.
Establishing tolerance to food involves various immune cells. Specific immune cells capture food particles, degrade them into smaller pieces, and display them to T cells in the immune system, signaling those cells to stay indifferent to the harmless invader. Recently, a minor fraction of cells — the RORγt+ dendritic cells — has been discovered among the gut’s presenting immune cells in several species. Colonna’s laboratory was the first to identify these cells in humans in 2023. Their function in preventing food allergies had not yet been investigated.
Patrick Rodrigues, PhD, a postdoctoral researcher, and Shitong Wu, an MD/PhD student in Colonna’s laboratory and co-first authors of the study, aimed to determine whether RORγt+ dendritic cells serve as the gut’s immune cells that avert food allergies. They administered ovalbumin, a highly allergenic protein found in egg whites, to mice both orally and intranasally. Mice lacking gut RORγt+ dendritic cells displayed signs of allergic lung inflammation, whereas those with these cells did not. Examination of gut immune cells revealed a disproportionate ratio between T cells that activate versus those that suppress immune responses to food particles in the allergic mice, leaning towards the former.
“By eliminating RORγt+ dendritic cells from the gut in mice, we disrupted tolerance to food allergens,” remarked Rodrigues. “This discovery now motivates us to investigate if we can achieve the opposite: prevent food allergies by enhancing the function of this cell population. Since RORγt+ dendritic cells are present in humans, our findings open up a promising avenue for managing food allergies and other gut-related immune disorders such as celiac disease or inflammatory bowel disease.”
Recently, the FDA approved an injectable treatment that, with continuous administration, helps avert an allergic reaction resulting from accidental exposure to trace amounts of allergens by blocking the antibodies produced from an invoked immune response. Avoiding allergens and carrying an EpiPen is still advised for patients using this medication.
“Targeting the activity of RORγt+ dendritic cells holds the potential to act even earlier to prevent an immune response from being initially triggered,” stated Wu. “If this hypothesis holds true, a therapy that supports the function of this small population of cells might provide enduring tolerance to food allergens.”
Rodrigues PF, Wu S, Trsan T, Panda SK, Fachi JL, Liu Y, Du S, de Oliveira S, Antonova AU, Khantakova D, Sudan R, Desai P, Diamond MS, Gilfillan S, Anderson SK, Cella M, Marco Colonna. Rorγt-positive dendritic cells are essential for the induction of peripheral Tregs in response to oral antigens. Cell. April 3, 2025. DOI: 10.1016/j.cell.2025.03.020
This research was funded by the National Institutes of Health (NIH), grant numbers RO1AI134035, RO1DK132327, RO1DK126969, RO1DK124699, T32DK077653; and the Swiss National Science Foundation (SNF), grant numbers P2BSP3_191754/P500PB_211033. The content reflects only the authors’ perspectives and does not necessarily represent the official views of the NIH.
About Washington University School of Medicine
WashU Medicine is a leading institution in academic medicine, focusing on biomedical research, patient care, and educational initiatives with a faculty of 2,900. Its National Institutes of Health (NIH) research funding portfolio ranks second largest among U.S. medical schools and has increased by 56% over the past seven years. In conjunction with institutional investments, WashU Medicine allocates over $1 billion annually towards fundamental and clinical research innovation and training. Its faculty practice consistently ranks among the top five nationwide, with more than 1,900 faculty physicians operating at 130 locations, also serving as the medical staff for Barnes-Jewish and St. Louis Children’s hospitals under BJC HealthCare. WashU Medicine has a distinguished history in MD/PhD education, recently dedicating $100 million to scholarships and curriculum improvement for medical students, and is home to outstanding training programs in all medical subspecialties, as well as physical therapy, occupational therapy, and audiology and communication sciences.
Originally published on the WashU Medicine website
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