Our bodies come equipped with a mechanism that naturally holds food allergies in check. A research team from Juntendo University and Hiroshima University has shown that a molecule called "soluble ST2," maintained at high levels in the blood, is what does the work, a finding that opens a new path for a condition that has long lacked a fundamental cure.

In Japan, roughly 1-2% of people have food allergies, and the figure reaches about 10% among infants.

Background: Why Do Food Allergies Occur?

Food allergy is a condition in which the immune system overreacts to foods that should be harmless. In recent years the number of patients has risen in developed countries, including Japan, and most cases begin in early childhood.

At its core is an immune response called "type 2 inflammation." When food antigens enter the body, epithelial cells are damaged and release a cytokine called IL-33 (interleukin-33). IL-33 activates various immune cells and triggers allergic symptoms.

IL-33's receptor, "ST2," comes in two forms: membrane-bound ST2 (ST2L) on cell surfaces, and soluble ST2 (sST2) in the blood and other fluids. When membrane-bound ST2 captures IL-33, it transmits a signal that promotes allergy. Soluble ST2, by contrast, was thought to act as a "decoy," capturing IL-33 and blocking that signal. But its actual role in the body had long been a mystery.

Solving the Mystery with Genetically Modified Mice

A collaborative team including Associate Professor Kumi Izawa, Professor Jiro Kitaura, and Center Director Ko Okumura of the Atopy Research Center at Juntendo University Graduate School of Medicine, together with Professor Susumu Nakae of Hiroshima University, took on the question.

They succeeded in creating genetically modified mice that express membrane-bound ST2 normally but lack only soluble ST2, making it possible to test the role of soluble ST2 directly.

Fibroblasts Hold the Key

The work produced several important findings.

First, "fibroblasts" in the skin and small intestine were found to produce far more soluble ST2 than mast cells, and to do so constantly. Fibroblasts are usually known as cells that support tissue structure, but they turned out to play a key role in suppressing allergy too.

Second, when food allergy was induced in mice lacking soluble ST2, symptoms were markedly worse than in normal mice. The number of mast cells in the small intestine, their degranulation rate (how often they release the substances that cause allergic symptoms), and levels of inflammatory cytokines such as IL-33 all rose.

More striking still, when "ST2-Fc," a substance that mimics soluble ST2, was given to the deficient mice, mast cell numbers and degranulation rates fell, and food allergy symptoms eased.

Hope for New Treatments

The findings were published in the Proceedings of the National Academy of Sciences (PNAS) on January 5, 2026.

The team points to several directions ahead. Drugs that selectively raise only the body's soluble ST2 are one promising approach, and molecular agents that block IL-33 signaling are also under consideration.

In fact, clinical trials of anti-IL-33 antibodies are already underway abroad, with results showing efficacy in peanut allergy patients. This study helps strengthen the scientific groundwork for such treatments.

IL-33 signaling is involved in many conditions beyond food allergy, including infections, tumors, cardiovascular disease, and metabolic disorders. The soluble ST2-deficient mice created here are expected to serve as a tool for clarifying soluble ST2's role in those diseases as well.

The Current State and Challenges of Food Allergies

In Japan, food allergy prevalence is about 10% in infants, 5% in three-year-olds, and 1.3-4.5% from school age onward. Eggs, milk, and wheat have traditionally been the three leading causes, but allergies to tree nuts (especially walnuts and cashews) have surged in recent years.

Current treatment rests mainly on avoiding the trigger food; no fundamental cure exists. Oral immunotherapy (gradually consuming small amounts of the trigger food to build tolerance) is being studied, but it does not work for every patient and carries risks of serious reactions such as anaphylaxis.

The role of soluble ST2 uncovered here could offer a new way through. Strengthening a defense the body already has may point toward safer, more effective treatments.

Food allergies are increasing worldwide, but trigger foods, access to treatment, and social responses differ greatly from country to country. In Japan, allergy-aware school lunches are spreading and food-labeling rules are in place, yet many challenges remain.

What is being done about food allergies in your country? Where do research and treatment stand? Please share your thoughts in the comments.

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