Asthmatic mice are protected from food-induced allergic reactions by means of an asthma medication.

In a groundbreaking discovery, a team of researchers led by Nathaniel Bachtel has identified genetic and cellular factors that influence susceptibility to severe food-induced anaphylaxis. The findings, published across two separate studies in Science, could pave the way for a potential therapeutic approach to treat food allergies.

The research, conducted over several years, focused on how allergen exposure through the mouth or gut influences allergic reactions in mice. The study found that a particular subset of mucosal mast cells in the intestine, which produce leukotrienes in response to allergens, play a critical role in oral anaphylaxis but not in systemic reactions.

Cysteinyl leukotrienes, a type of inflammatory molecule, were found to be particularly significant in this process. Excess leukotriene D4 (LTD4) in the gut is suggested to enhance the movement of allergens from the gut lumen into the tissue, triggering anaphylactic reactions.

The discovery of this new pathway came after a years-long forward genetic screen. The research linked this difference to genetic variants in an enzyme dipeptidase 1 (DPEP1), which breaks down LTD4. Mice resistant to anaphylaxis had a more active version of DPEP1, allowing them to degrade LTD4 more efficiently in the small intestine. In contrast, susceptible mice had less active DPEP1, leading to higher LTD4 levels.

The team found that blocking CysLT production using Zileuton, an FDA-approved drug for the treatment of asthma, reduced anaphylaxis after oral allergen exposure. This could offer a new approach to treat food allergies, as a simple pill that temporarily shields allergic individuals by blocking the body's anaphylactic pathway before it activates.

The Northwestern team has launched a small early-stage clinical trial to test whether blocking the newly identified pathway with Zileuton in humans is effective. The findings suggest that food-specific immunoglobulin E (IgE) is the central mediator of anaphylactic reactions, but some people with IgE to food allergens can ingest these foods without having symptoms, a phenomenon known as "sensitized tolerance" or "asymptomatic sensitization."

Other conditions capable of driving leukotriene excess in the intestines or ILC2 activation may act as cofactors toward the development of severe anaphylactic responses to foods. The reports by Hoyt et al. and Bahtel et al. offer "hope of a potential therapeutic approach for treating food allergy." This breakthrough wouldn't have been possible without long-term investment in scientific research.

Asthmatic mice are protected from food-induced allergic reactions by means of an asthma medication.