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that early-life exposure to an allergen can prevent the development of allergy later on. The findings, published in Frontiers in Immunology, also shed light on similar processes in humans and lend support to long-standing theories about how the immune system learns to tolerate environmental challenges.
The research focused on hypersensitivity to Culicoides midges; tiny blood-feeding insects whose saliva contains proteins capable of triggering intense allergic reactions in horses. Affected animals may suffer from severe itchiness, hair loss, dermatitis, and, in extreme cases, weight loss. Icelandic horses are particularly vulnerable once they leave their native environment because Culicoides species do not exist in Iceland. As a result, horses exported later in life often encounter midges for the first time abroad and may develop what is commonly known as “sweet itch.”
Lead researcher Dr. Bettina Wagner, James Law Professor of Immunology at Cornell’s College of Veterinary Medicine, had long been intrigued by anecdotal reports from breeders. “The rumour was that adult Icelandic horses exported to Europe developed Culicoides allergy far more often than those bred there,” she explained. Later epidemiological studies confirmed these observations, prompting Wagner and her team to investigate when and why allergic reactions occur.
Their 13-year study followed several cohorts of related Icelandic horses living together under identical environmental conditions at Cornell. The crucial difference among groups lay in the timing of first exposure to Culicoides and whether foals received allergen-specific maternal antibodies. Since Culicoides do not exist in Iceland, the imported horses provided a uniquely “naïve” population, free from prior exposure.
The results were striking. Horses experiencing Culicoides bites for the first time in adulthood showedmthe highest rates of hypersensitivity. 62.5% went on to develop the characteristic eczema-like symptoms. When first exposed during adolescence, only 21.4% developed allergy. Yet none of the horses exposed from birth ever showed signs of Culicoides hypersensitivity, despite having a genetic predisposition: all full-siblings had at least one allergic parent.
These findings strongly support the idea that early exposure to an allergen can “train” the developing immune system to tolerate it. On the Cornell Chronicle website, Wagner explains that during early development, immune responses are more flexible and more capable of learning to recognise otherwise reactive substances as harmless. “Training of the immune system to develop tolerance against allergens early in life creates a specific ability to adjust to those allergens and recognise them as harmless,” she said. “The earlier it happens, the more successful it is.”
In humans, similar concepts underlie the well-known hygiene hypothesis - the observation that children raised in environments rich in microbes and animal exposures tend to have fewer allergies than those raised in more sanitized conditions. Because horses share many features of immune function with humans, the study contributes important evidence to understanding how early-life environmental contact shapes lifelong immune health.
The study also tested whether maternal antibodies, specifically allergen-specific Immunoglobulin E (IgE) and Immunoglobulin G (IgG), played a role in determining allergy outcomes. Previous observations suggested that allergic mothers might pass IgE to their offspring, increasing the likelihood of allergy. However, the Cornell study found no such effect. Foals born to mares carrying Culicoides-specific IgE did not show higher allergy rates, nor did maternal antibodies appear to protect against or predispose foals to hypersensitivity.
By following the horses for at least nine years of repeated seasonal exposure, the researchers were able to firmly establish that early-life exposure, not maternal immunity, was the determining factor in whether hypersensitivity developed.
The work was led by first author Dr. Elisabeth Simonin, a postdoctoral researcher in Wagner’s laboratory, with collaborators from the University of Iceland, Cornell technicians, and veterinary students. The study was supported by the Harry M. Zweig Memorial Fund for Equine Research, which funded both the importation of the Icelandic herd and their long-term maintenance.
For equine scientists, these results highlight the importance of developmental timing in immune system training and raise questions about how management practices, especially for horses moved between environments, may influence long-term health. More broadly, the research offers a powerful example of how equine models can advance understanding of allergy mechanisms relevant to multiple species, including humans.
Early allergen introduction overrides allergy predisposition in offspring of horses with Culicoides hypersensitivity
Frontiers in Immunology (2025)
Vol 16 . 1654693
https://doi.org/10.3389/fimmu.2025.1654693
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