The Role of Immune Cells in Food Allergy Prevention

The immune system serves as the body’s defense network, designed to rapidly detect and eliminate harmful pathogens such as viruses, bacteria and other foreign invaders to prevent illness. At the same time, it must carefully distinguish between dangerous threats and harmless substances, like pollen, dust or certain foods. When this balance is disrupted and the immune system reacts to non-threatening stimuli, allergic responses can occur.

A new study led by researchers at NYU Langone Health has revealed that a special group of cells found in mouse intestines suppresses the immune responses caused by food protein exposure. These “tolerogenic dendritic cells” enable food to pass through the body without triggering an immune reaction unless they malfunction to cause allergies. The study was published in Nature.

Unraveling the immune system’s role in food allergies

Food allergies occur when the immune system mistakenly identifies a specific food or a substance within that food as a threat, triggering an inappropriate immune response. This response involves the production of immunoglobulin E antibodies, which bind to the perceived allergen and prompt immune cells to release histamine and other inflammatory chemicals. These substances cause the classic allergic reaction symptoms, ranging from mild itching or hives to life-threatening anaphylaxis.

It is important to distinguish between food allergies and intolerances. Although both can lead to unpleasant symptoms after eating certain foods, the underlying mechanisms differ significantly. Food allergies involve the immune system and can be severe and even fatal. On the other hand, food intolerances typically result from difficulty digesting certain ingredients, such as lactose or gluten, and usually produce milder, non-immune-related symptoms like bloating or stomach cramps.

Under normal conditions, the immune system is trained to tolerate harmless substances, including components of the body’s own tissues and benign environmental molecules such as food proteins. This process, known as immune tolerance, prevents the immune system from overreacting to non-threatening exposures. While self-tolerance – ignoring the body’s healthy cells – is well understood, the mechanisms that govern tolerance to foreign but harmless substances like food have remained unclear.

Recent research led by Dr. Dan Littman, the Helen L. and Martin S. Kimmel Professor of Molecular Immunology in the Department of Pathology and a professor in the Department of Cell Biology at NYU Grossman School of Medicine, has helped uncover how the immune system learns to distinguish between harmful invaders (e.g., pathogens) and everyday exposures like food, offering new insights into the prevention and treatment of food allergies.

Key proteins are also needed to protect against the immune response

By studying mice, the researchers identified tolerogenic dendritic cells – a type of immune cell that presents antigens on their surface for notice by T cells – that allow food to pass through the body without triggering an immune response unless they malfunction and cause allergies.

When the tolerogenic dendritic cells present antigens from food or friendly microbes to T cells, the T cells become anti-inflammatory or “regulatory.” Therefore, the next time the T cell encounters the antigen, instead of attacking, it will suppress nearby inflammation.

The researchers found that, without these cells, mice had fewer regulatory T cells to prevent inflammation and more inflammatory T cells, leading to allergies and inflammation when exposed to antigens.

Littman and team also found the cells to require the proteins Retinoic Acid–Related Orphan Receptor-gamma-t (RORγt) and PR domain–containing 16 (Prdm16) to effectively protect tolerated food proteins from the inrush of immune cells meant to destroy foreign cells.

The team previously identified these same cells to control immune tolerance to gut-friendly bacteria – although little was known about their identity and whether they controlled tolerance to anything else in the gut. 

“Our study shows that RORγt-expressing dendritic cells are key components in the immune regulatory response that prevents food allergies,” said Littman, also a Howard Hughes Medical Institute Investigator.  

“This discovery adds evidence to our earlier work showing that these cells also keep the peace with the vast microbiome, the mix of microbes that inhabits our body, and may be important for preventing autoimmune conditions like Crohn’s disease,” he continued.

Less is known about the human equivalent of tolerogenic dendritic cells

Through analyzing human intestinal tissue and public sequencing datasets, Littman and team discovered the human equivalents of tolerogenic dendritic cells. Although it is not yet clear how abundant these cells are or whether they are involved in other forms of immune tolerance outside the intestines, this should be made easier by the comprehensiveness of the research completed to identify the new cells.

“If further experiments prove successful, our findings could lead to innovative ways to treat food allergies,” Littman said. “For example, if someone has a peanut allergy, perhaps we can use tolerogenic dendritic cells to help create more regulatory T cells to suppress an allergic response to peanut molecules.”

Moving forward, the researchers also want to understand more deeply how and where tolerogenic dendritic cells develop in the body and what kinds of signals they need to receive to perform their function.

Reference: Fu L, Upadhyay R, Pokrovskii M, et al. Prdm16-dependent antigen-presenting cells induce tolerance to gut antigens. Nature. 2025:1-3. doi: 10.1038/s41586-025-08982-4

This article is a rework of a press release issued by NYU Langone Health. Material has been edited for length and content.