Researchers have uncovered a likely origin of our allergies

If you suffer from seasonal allergies, a move to a far-flung location can deliver a reprieve. But in many cases, it’s only a matter of time before the new environment's changing seasons elicit itchy eyes and a runny nose. Photo / 123rf

While bacteria and viruses set off immediate alarm in our immune system, allergies follow a different path.

If you suffer from seasonal allergies, a move to a far-flung location can deliver a reprieve from the pollens and moulds that caused you torment. But in many cases, it’s only a matter of time before this new environment’s changing seasons elicit itchy eyes and a runny nose. Researchers have uncovered a probable origin story for emerging and reemerging allergies.

Exposure to bacteria or viruses typically sets off immediate alarm bells in the immune system, provoking a response to repel the infectious intruder. Allergies arise through a distinct branch of the immune system and unfold differently, according to immunologist Caroline Sokol, who wrote the paper along with postdoctoral fellow Xueping Zhu at the Ragon Institute of Mass General Brigham, MIT and Harvard University, and other scientists. In this context, repeated exposure over time to small amounts of a particular allergen gradually develops into a full-blown allergy.

In a 2020 study, Sokol’s team traced the initiation of environmental allergic reactions to a surprising source: sensory neurons. Responsible for our sense of touch, these neurons are among the first to interact and communicate with the allergic immune system, Sokol said in a video interview. “Sensory neurons respond directly to allergens … by inducing an itch response,” she added.

But until Sokol and her team published a study last month in the journal Cell, it remained unclear how this response builds over time. “The hypothesis was just: What if the neurons are developing a ‘memory’ of this allergen?” she said. “So we tried to build a model to look at it, and that’s what we found.”

The researchers exposed mice to triggers, including the papaya-derived compound papain and dust mite allergens, and then examined how their sensory neurons responded. These exposures put the animals’ neuronal mitochondria, tiny structures that generate energy to power cells, into a “primed” and hypervigilant state. After additional allergen encounters, these cells triggered an even stronger immune response and more severe itching.

This priming was not tied to a specific allergen. Mice initially exposed to papain also experienced a stronger reaction when treated with dust mite or mould allergens. That means this mechanism could give rise to a broad range of allergies over time. “Anything that could activate the same pathway activates this memory response,” Sokol said. This could explain why many people acquire allergies to a range of substances.

This study specifically focused on a particular aspect of allergic reaction in animals – skin inflammation and itching. But Sébastien Talbot, a neuro-immunologist at Queen’s University in Kingston, Ontario, who was not involved with the study, said its findings are likely to be relevant in humans based on known similarities in physiology between the two species.

“This body of work has been super interesting and really shows that neurons are at the centre of mounting allergic immunity,” he said.

Talbot adds that researchers have observed a similar mechanism in how mice experience chronic pain, in which sensory neurons can become primed to generate an excessive immune response that leads to uncontrolled, painful inflammation.

Sokol and her colleagues are trying to better define how this sensitisation is established and identify factors that determine whether allergies ultimately take hold. But their work has already revealed a protein in the mitochondria that plays a central role in this process, and she is enthusiastic about the possibility of developing drugs that directly target the mechanisms underlying allergies. “Can we reverse it? These are important things that we’re testing,” she said.