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,” Sokol said. “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.”
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.
Authorship: In addition to Sokol, Mass General Brigham authors include Xueping Zhu, Haibo Yang, Haoting Zhan, Isabela J. Kernin, Dean R. Buttaci, Ngoc Le, Cai Han, Parth R. Naik, Peri R. Matatia, Sarah Zaghouani, Lillian R. Delacruz, Lukas M. Altenburger, Neal P. Smith, Elena Wu, Rebecca Londoner, Cameron H. Flayer, Zhengwang Sun, Alison E. Ringel, Alexandra-Chloe Villani, and Rod A. Rahimi.
Disclosures: Sokol is a paid consultant for Bayer, Merck and Lilly; has received sponsored research support from GSK; and serves on the scientific advisory board for Granite Biosciences and the advisory board for Immunity . Additional author disclosures can be found in the paper.
Funding: This study was funded in part by the National Institutes of Health (R01AI202406, 1S10OD036287), the Food Allergy Science Initiative, a Massachusetts General Hospital Howard M. Goodman Fellowship, the Gene Lay Institute of Immunology and Inflammation, and a Gene Lay Institute of Immunology and Inflammation Fellowship.
Paper cited: Zhu X et al. “Sensory neuronal mTORC1 kinase signaling establishes neuroimmune memory that initiates allergic immunity,” Immunity DOI: 10.1016/j.immuni.2026.08.012
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Immunity
Observational study
People
Sensory neuronal mTORC1 kinase signaling establishes neuroimmune memory that initiates allergic immunity
22-Sep-2026
Sokol is a paid consultant for Bayer, Merck and Lilly; has received sponsored research support from GSK; and serves on the scientific advisory board for Granite Biosciences and the advisory board for Immunity. Additional author disclosures can be found in the paper.