Sensory neurons remember past allergens to trigger future allergic reactions

Mass General Brigham researchers found that sensory neurons retain a 'memory' of allergens that may help explain why allergies develop over time.

A new preclinical study led by investigators from Mass General Brigham offers a potential explanation for two longstanding questions in allergy: why do allergies often emerge only after repeated exposure, and why do people with one allergy frequently develop others? The findings are published in Immunity.

The team's earlier work revealed that sensory neurons - the nerve cells that allow us to feel sensations such as itch and pain - can directly sense certain allergens and help start the allergic immune response. The new study shows that these neurons do not simply detect allergens in the moment but can retain a metabolically encoded record - or "memory" - of previous exposures that allows them to respond more strongly to later exposures, even after the original allergen is gone.

"Now that we know what may cause people to become allergic and pick up more sensitivities, we can design ways to stop it from happening," said senior author Caroline L. Sokol, MD, PhD, a physician-scientist in the Division of Allergy and Clinical Immunology in the Mass General Brigham Department of Medicine. Sokol is also a member of the Ragon Institute of Mass General Brigham, MIT, and Harvard and a core member of the Gene Lay Institute of Immunology and Inflammation. "What is especially encouraging is that allergic memory in neurons faded with time in our models. We are now investigating whether we can deliberately reset this memory, which could ultimately offer a way to reduce the risk of developing allergies."

The study grew from a familiar clinical observation – people tend to encounter the same pollen, pets, or foods repeatedly before developing an allergy. Drawing on her perspective as a clinician, scientist, and allergy sufferer, Sokol wondered whether the nervous system might help explain this delay.

Neurons are known for their ability to form memories. We asked whether an initial allergen exposure might leave a trace – not enough on its own to trigger a full allergic response, but enough to prime the neurons to respond more strongly the next time."

Caroline L. Sokol, MD, PhD, a physician-scientist, Division of Allergy and Clinical Immunology, Mass General Brigham Department of Medicine

To test this idea, the researchers modeled recurrent allergen exposure in mice and found that an initial exposure activates a specific signaling pathway in neurons. This pathway not only primes them to later respond to the same allergen, as the team hypothesized, but also to other allergens that share the same enzymatic activity but have different molecular structures. This suggests that sensory neurons may remember a shared feature of allergens – the type of danger signal they produce – rather than their precise molecular identity. This cross-allergen response may help explain why developing sensitivity to one allergen can increase susceptibility to others.