🧬 Our bodies have a hidden guardian that naturally suppresses food allergies.
In Japan, approximately 1-2% of the population suffers from food allergies, with rates reaching about 10% in infants. For this condition that has long lacked a fundamental cure, researchers at Juntendo University and Hiroshima University have made a groundbreaking discovery. A molecule called "soluble ST2" (sST2), naturally maintained at high levels in the body, has been found to suppress food allergies.
Background: Why Do Food Allergies Occur?
Food allergy is a condition where the immune system overreacts to foods that should normally be harmless. In recent years, the number of patients has been increasing in developed countries including Japan, with most cases occurring in infancy.
The development of food allergies is deeply connected to 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). This IL-33 activates various immune cells and triggers allergic symptoms.
IL-33 has a receptor called "ST2," which exists in two forms: membrane-bound ST2 (ST2L) on cell surfaces, and soluble ST2 (sST2) present in blood and other bodily fluids. When membrane-bound ST2 captures IL-33, it transmits signals that promote allergies. On the other hand, soluble ST2 was thought to act as a "decoy," capturing IL-33 and inhibiting signal transmission. However, the actual role of soluble ST2 in the body had long remained a mystery.
Solving the Mystery with World's First Genetically Modified Mice
A collaborative research team including Associate Professor Kumi Izawa, Professor Jiro Kitaura, and Center Director Ko Okumura from Juntendo University Graduate School of Medicine's Atopy Research Center, along with Professor Susumu Nakae from Hiroshima University, took on this challenge.
The research team succeeded in creating the world's first genetically modified mice that express normal membrane-bound ST2 but lack only soluble ST2. This made it possible to directly verify the true role of soluble ST2.
Surprising Discovery: Fibroblasts Hold the Key
The research yielded several important findings.
First, it was discovered that "fibroblasts" in the skin and small intestine constantly produce more than 10 times the amount of soluble ST2 compared to mast cells. Fibroblasts are typically known as cells that support tissue structure, but they were also found to play a crucial role in allergy suppression.
Second, when food allergies were induced in mice lacking soluble ST2, the allergic symptoms were significantly worse compared to normal mice. Specifically, the number of mast cells in the small intestine, their degranulation rate (the rate at which they release substances that cause allergic symptoms), and the expression levels of inflammatory cytokines like IL-33 all increased.
Even more interestingly, when a substance called "ST2-Fc" that mimics soluble ST2 was administered to the soluble ST2-deficient mice, the mast cell numbers and degranulation rates decreased, and food allergy symptoms were suppressed.
Hope for New Treatment Development
These research findings were published in the Proceedings of the National Academy of Sciences (PNAS) on January 5, 2026.
According to the research team, several future possibilities are being considered.
Developing drugs that selectively increase only soluble ST2 in the body is one promising approach. Development of molecular biological agents that inhibit IL-33 signaling is also being explored.
In fact, clinical trials using anti-IL-33 antibodies are already underway overseas, with results showing efficacy in peanut allergy patients. This Japanese research represents an important step in strengthening the scientific foundation for such treatment development.
Furthermore, IL-33 signaling is involved in many conditions beyond food allergies, including infections, tumors, cardiovascular diseases, and metabolic disorders. The soluble ST2-deficient mice created in this study are expected to become important tools for understanding the role of soluble ST2 in these diseases.
The Current State and Challenges of Food Allergies
In Japan, the prevalence of food allergies is approximately 10% in infants, 5% in 3-year-olds, and 1.3-4.5% in school-age children and older. While eggs, milk, and wheat have traditionally been the three major causes, tree nut allergies (especially walnuts and cashews) have been rapidly increasing in recent years.
Current food allergy treatment is primarily based on avoiding the causative foods, and no fundamental cure has been established. Oral immunotherapy (a method of gradually consuming small amounts of the causative food to develop tolerance) is being researched, but it is not effective for all patients and carries risks of serious adverse reactions such as anaphylaxis.
The role of soluble ST2 revealed in this research may provide a new approach to overcome this situation. The concept of enhancing the body's natural defense mechanisms could lead to the development of safer and more effective treatments.
Conclusion: What's the Food Allergy Situation in Your Country?
Food allergies are increasing worldwide, but the causative foods, access to treatment, and social responses vary greatly by country. In Japan, allergy-friendly school lunches are becoming more common and food labeling systems have been established, but many challenges remain.
This Japanese research finding may offer hope to food allergy patients around the world. What kind of measures are being taken against food allergies in your country? What is the status of research and treatment development? Please share your thoughts in the comments!
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Reactions in Japan
It's truly groundbreaking that the mechanism for suppressing food allergies has been discovered! My child struggles with egg allergies, so I hope this research gets practical applications soon. Japanese university research capabilities are really impressive.
Since it's still at the mouse experiment stage, it'll probably take more than 10 years before it can be applied to humans. We shouldn't get our hopes up too much. But I do think it's an important finding as basic research.
I've always been anxious during school lunch time, but thanks to research like this, there may come a day when children can enjoy meals more freely. Thank you to all the researchers.
IL-33 targeted therapies are already in clinical trials overseas. This research offers a new approach with sST2. I'm watching to see how pharmaceutical companies will respond.
It was surprising that fibroblasts are the main source of sST2 production. Mast cells have been the focus until now, but it's fascinating that cells supporting tissue structure are also involved in immunity.
Seeing how the IL-33 pathway I learned about in textbooks connects to actual research like this really motivates me to study! Someday it will be useful in clinical practice.
Food allergy management is a major challenge for the food industry too. If treatments are established, allergen labeling and regulations on specific ingredients might change.
As an adult who still has a peanut allergy, I'm really grateful for research like this. It's exhausting to ask 'Does this contain peanuts?' every time I eat out...
Joint research by Juntendo and Hiroshima Universities. The method of creating genetically modified mice with CRISPR/Cas9 is also noteworthy. This is proof that Japan's genome editing technology is steadily advancing.
The research is wonderful, but I'm worried about the path to practical application. Clinical trials won't progress without pharmaceutical investment, and I hope Japanese technology doesn't get taken overseas.
More children with allergies are coming to our nursery, and managing meals is really challenging. I'm always nervous about accidental ingestion. If treatments become available in the future, children, parents, and we caregivers could all feel relieved.
If drug development targeting sST2 progresses, long-term treatments like oral immunotherapy might no longer be necessary. I'm hopeful about reducing the burden on patients.
This is the kind of basic research that deserves national funding. Even if results don't come immediately, it has the potential to change medicine in 10 or 20 years. This reminds me of the importance of research grants.
I overcame my egg allergy through oral immunotherapy, but eating small amounts every day was really hard. It would be amazing if there was a treatment that could cure it with just one injection.
It's a groundbreaking discovery, but if it becomes a biologic drug, I'm worried about the price. If it costs hundreds of thousands of yen a month like in America, ordinary people won't be able to use it. We need discussions about insurance coverage.
Japanese researchers are always at the forefront of allergy research! My son has a peanut allergy and in America, we have to send him to school with an EpiPen. I hope this research gets clinical applications soon.
As an immunologist, I believe this research significantly advances our understanding of the sST2 pathway. The finding that fibroblasts are the main source of production was unexpected. Our lab is considering replication studies.
In France, more children have food allergies and managing school meals has become a social issue. If Japanese research leads to new treatments, families around the world will be helped.
Awareness of food allergies is still low in Singapore. I hope that media coverage of this research will help spread understanding of allergies.
Excellent research, but there's a long road from mouse experiments to human application. We shouldn't get our hopes up too much. Still, it's valuable that it shows new possibilities for food allergy treatment.
Australia has one of the highest rates of food allergies in the world. Our researchers are also studying the IL-33 pathway, but the Japanese team's genetically modified mouse approach is innovative.
In the UK, food labeling laws were strengthened after a tragic case where a girl died from a severe allergic reaction. I hope research like this leads to fundamental solutions.
In Mexico, access to food allergy diagnosis is limited. I hope research achievements in developed countries will eventually benefit emerging countries like ours.
In India, awareness of food allergies is low, and many patients are dismissed as just being 'picky eaters.' I hope the development of international research will influence medical practice in our country.
I work at a Swiss pharmaceutical company, and sST2 has been getting attention as a biomarker for heart failure. Applying it to food allergies is a new perspective. I'm watching future developments closely.
Oral immunotherapy is common in Canada, but treatment takes years and has risks of side effects. I hope new approaches like this research lead to safer and more effective treatments.
The number of children with food allergies is also increasing in Korea. We always pay attention to Japanese research achievements. I hope Korean and Japanese researchers can collaborate on studies specific to Asian populations.
In the UAE, allergies are increasing along with westernized diets. We would like to build collaborative relationships with Japanese research institutions. More international cooperation is needed in this field.
In Brazil, we don't even have sufficient statistical data on food allergies. I hope research from developed countries will influence medical policies in our country and improve support for allergy patients.
As a father in New Zealand, I'm always mindful of my children's allergies. When this research gets commercialized, I hope it will be affordable and accessible in all countries.