A "groundbreaking" discovery from Wellington's Malaghan Institute of Medical Research has highlighted a missing piece in the link between the skin and the development of allergies.
Termed the most important immunological discovery from New Zealand in 20 years, the research has found a molecule constantly present in the skin that favours allergic reaction.
For the past decade immunologists have been aware that exposure to allergens through the skin affected a person's predisposition to food allergies.
But the discovery of a molecule called IL-13 shows why the skin might be primed to allergic response.
Lead researcher and immunologist at the Malaghan Institute Professor Franca Ronchese said they had previously thought IL-13 was only created in the skin when necessary.
"What we found is that in the skin it's always made, and somehow conditions our immune response system to whatever we are exposed to through the skin, favouring allergic responses.
"It's only made in the skin, in healthy people – not in the lung, not in the gut or other parts of our body – it seems to be specific to skin.
"And what this means is whatever we are exposed to through the skin is more likely to result in an allergic response."
IL-13 is a molecule made when immune cells are alerted to cellular damage from allergens or parasites – when released, it acts as a switch which triggers an imflammatory response.
Ronchese's research has shown that IL-13 only exists in the skin, and is constantly produced.
This helps to explain recent studies that had shown development of food allergies in children who had never eaten the food, but had only been exposed to it through their skin.
Ronchese said the most common allergies in New Zealand were atopic dermatitis – affecting 25 per cent of children, and 9 per cent of adults – and allergic asthma, affecting 9 per cent of New Zealanders.
"We've known that skin is a little bit special when it comes to allergies.
"We had an inkling this might be the case from those studies about food allergies, but it wasn't clear why – there was no cause and no reason for this.
"And we think we have found that by finding the IL-13, made only in the skin, and not in other parts of the body."
Funded by the Health Research Council of New Zealand, the project has been carried out by a team of 25 over a period of five years, with significant contribution from Malaghan Institute researchers Dr Johannes Mayer and Olivier Lamiable.
Ronchese said they had tested common allergens such as house dust mite on mice, and made the discovery of IL-13 early on in their research.
"Some of the experiments we do is like a bit of detective work.
"We find a piece of evidence but we have to prove it before we are sure, and that work can take a very long time.
"We were lucky that all the evidence we found was very consistent and all pointed to that IL1-3."
Malaghan Institute director Professor Graham Le Gros said the detection of IL-13 was "the most important immunological discovery to come out of New Zealand in the past 20 years".
"It marks a milestone in fundamental immunology which will have far-reaching impacts in the design and development of immunotherapies that target allergic and inflammatory conditions."
Clinical immunologist Dr Maia Brewerton said the importance of the skin as a mechanism for food allergy had become well-recognised within the past decade, but there were still many unknowns.
"Now I think it's well-accepted or recognised that sensitization to food antigens through the skin is a really important mechanism of food allergy," said Brewerton, who has just stepped down as chairwoman of the New Zealand Clinical Immunology and Allergy Group.
"But we still don't fully understand what's happening in the skin that means that if you're exposed to an allergen through the skin, you're more likely to be sensitized to it.
She said New Zealand should feel proud of Ronchese's important immunological discovery.
"Franca's piece could really be the piece in the jigsaw puzzle we're looking for – it really is a ground-breaking discovery and so it will be really important, internationally, in understanding allergy and sensitization.
"We've got all this clinical data but we couldn't explain what was happening in the skin, or why this would be happening in the skin, or what was the difference in the immune responses.
"Her work is really getting into the nitty-gritty of the immune cells in the skin and how they might differ, or how they might be primed in a different way to sensitise to certain food products."
While findings in immunology suggested links between skin exposure to allergens and the development of food allergy, Brewerton said there was still much to learn.
But she suggested people be cautious about what they put on their skin.
"I think it's important that parents don't panic, as we don't have all the knowledge yet," she said.
"One of the pieces of advice that I give is that food belongs in our mouth, not on our skin. Because we don't understand yet what all the factors are that might put you at risk, it's important that people understand that."
Ronchese said the discovery of IL-13 could enable us to better teach our immune systems how to respond to allergens – through the mouth, rather than the skin.
"Understanding that the skin is predisposed to allergies suggests that we have to educate our immune system in a different way.
"Your body can't learn what is good for it if it's never encountered it, and perhaps we need to consider the manner in which we introduce these materials to the body.
"We have to give it an opportunity to learn what this food is by eating it."
While there were still many gaps in the understanding of allergies the discovery of IL-13 narrowed down the target on what immunologists were trying to understand, Ronchese said.
"The disease is becoming so common and we don't have a cure, and it has such an impact on our lifestyle.
"Not having a cure means you have to avoid allergens. We really need to make some traction in this field so we were very happy to find something that we can finally put our finger on – this IL-13.
"And we have to try to understand why we make it, and what we can do to maybe stop it if possible."
The paper, entitled Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote Th2 and inhibit Th17 cell polarization, has been published in Nature Immunology.