Most of the time, the intestinal immune system can recognize friend from foe, tolerating myriad foods while destroying disease-causing invaders. But for approximately 30 million Americans with food allergies — including 4 million children — immune cells mistakenly identify food as a threat, triggering potentially life-threatening reactions.
Now, researchers at Washington University School of Medicine in St. Louis have identified, in mice, that essential immune cells in the intestine prevent an unwarranted attack against harmless food allergens. In the absence of such cells, mice experienced gut inflammation and an allergic response to food.
Their research was published online April 3 in Cell and will appear in print May 15.
“We are seeing a rapid global increase in food allergies that significantly impact quality of life,” said Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology at WashU Medicine. “The lack of therapeutics to prevent and manage food allergies complicates the growing public health issue. Now that we know the players that establish tolerance to food allergens, we can devise innovative strategies to target them therapeutically and potentially prevent or treat food allergies.”
The immune system encounters common food allergens — peanuts, tree nuts, milk, eggs and shellfish, among others — without launching a self-sabotaging immune attack in a process called tolerance. Broken tolerance to food triggers an allergic reaction with symptoms ranging from mild hives and itching to a severe, life-threatening allergic reaction that can cause throat swelling and difficulty breathing and requires immediate treatment. As part of the current study, the researchers aimed to home in on the players working to prevent such reactions, in work that may help develop preventive treatments for food allergies.
Tolerance to food involves multiple immune cells. Certain immune cells pick up food particles, chop them into fragments and present them to the immune system’s T cells, instructing those cells to remain unresponsive to the harmless intruder. More recently, a small population of cells — the RORγt+ dendritic cells — has been found among the gut’s presenting immune cells in multiple species. Colonna’s lab was the first to identify the cells in people in 2023. Their role in preventing food allergies had not been explored.
Patrick Rodrigues, PhD, a postdoctoral scholar, and Shitong Wu, an MD/PhD student, in Colonna’s lab and the study’s co-first authors, set out to understand whether RORγt+ dendritic cells are the gut’s immune cells that prevent food allergies. They treated mice with ovalbumin, a highly allergenic protein found in egg whites, orally and then intranasally. Mice lacking gut RORγt+ dendritic cells showed signs of allergic lung inflammation, while mice with these cells did not. An analysis of the gut immune cells found an imbalance among the T cells that trigger versus dampen immune responses to food particles in the allergic mice, with a skewing toward the former.
“By removing RORγt+ dendritic cells from the gut in mice, we broke tolerance to food allergens,” said Rodrigues. “The discovery is now inspiring us to see if we can do the opposite: prevent food allergies by supporting the activity of this cell population. Because RORγt+ dendritic cells are found in people, our finding presents an exciting new possibility to manage food allergies and other gut-related immune diseases such as celiac disease or inflammatory bowel disease.”
Recently, the FDA approved an injectable medication, that, if administered continuously, helps prevent an allergic response to accidental exposure to small amounts of allergens by blocking the antibodies that result from an activated immune response. Avoiding the allergen and carrying an EpiPen is still recommended for individuals on the medication.
“Targeting the activity of RORγt+ dendritic cells has the potential to work even further upstream to prevent an immune response from first being triggered,” said Wu. “If that proves to be true, a therapy supporting the activity of this small population of cells might offer lasting tolerance to food allergens.”
