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Fighting allergic skin disease at its root

17 December 2024

Dr Sotaro Ochiai’s research is uncovering why and how atopic dermatitis develops on a cellular level. He aims to identify therapeutic targets which may be able to dampen the overactive immune cells present in the skin of those affected.

“Some of my earliest memories are of itching,” says Dr Sotaro Ochiai, a Postdoctoral Research Fellow in the Ronchese Laboratory at the Malaghan Institute.

“There’s a relentless irritation that demands your attention, distracting you from functioning until you finally give in and scratch. Scratching, although it brings fleeting relief, makes everything worse.”

Sotaro has lived with atopic dermatitis, a type of eczema, for as long as he can remember. Coming in waves of varying severity, the chronic skin condition starts as itchy, dry skin, which thickens and hardens, sometimes cracking. This can progress into angry, red rashes which can ooze clear fluid or blood.

“Winters can be brutal, with dry air making my skin crack and bleed, while summer often brings heat rashes,” says Sotaro.

“I think the worst symptom was how much it affected my self-confidence, especially when I was a teenager.”

More than a third of Aotearoa New Zealand’s population is afflicted by atopic dermatitis.

Current treatments are mainly corticosteroid creams which provide temporary relief but with many side-effects.

“Atopic dermatitis is an allergic disease caused by an overactive immune response in the skin. Though so many people live with this debilitating condition, we still don’t know why and how it develops.”

“We are ultimately working towards developing new treatments to manage atopic dermatitis by modulating the activity of tissue-resident memory T-cells in the skin.”

Sotaro’s research is uncovering the cellular processes that drive atopic dermatitis.

“The skin is a very important site when it comes to allergies. Previous work in our lab indicates that it could be the first site of allergic disease development as the early immune system learns to identify what is a threat and what is harmless,” says Sotaro.

Our skin is our largest organ and serves as a vital barrier, protecting us from harmful substances in the environment. However, in some people, especially at a young age, harmless allergens like dust mites or peanut proteins can breach this barrier. When this happens, the immune system springs into action, triggering inflammation to eliminate the perceived threat.

In the process, it forms specialised immune cells called tissue-resident memory T-cells which remain in the skin to ‘remember’ the allergen. If the skin encounters the allergen again, these tissue-resident memory T-cells mount a faster and more intense response.

“While this mechanism is vital for fighting against real threats, it becomes problematic when the allergen is harmless and frequently encountered, leading to skin conditions such as atopic dermatitis,” says Sotaro.

Sotaro’s research focuses on finding ways to reduce the severity of skin allergic reactions, by targeting tissue-resident memory T-cells in the skin.

“To do this, we are trying identify proteins produced by the body that are crucial for the survival of allergy-inducing tissue-resident memory T-cells in the skin, but not other cells in the body.”

This is like finding a needle in a haystack of millions of protein configurations. Luckily, Sotaro and the team have just the tools to do such a thing.

“With the help of bioinformatics and data science tools, we can find and narrow down potential targets to test.”

Sotaro will then disrupt the production of the identified targets in skin cells from donors with atopic dermatitis and observe the effect this has on the function of tissue-resident memory T-cells.

“We are ultimately working towards developing new treatments to manage atopic dermatitis by modulating the activity of tissue-resident memory T-cells in the skin.”

“There’s still so much we don’t understand when it comes to allergies, yet the need to know is urgent as the incidence of allergies are increasing every year.”

Sotaro's life-long experience with atopic dermatitis is what first motivated him to become an immunologist.

Sotaro spent his formative years in Fukuoka, Japan and first came to Aotearoa New Zealand on an exchange programme to play rugby.

“I just loved it here and I was sad to leave. However, a year later I moved to Auckland with my family. I didn’t speak English when I first came but rugby transcended all language and I was able to make friends quickly. The rest is history”

Settling into Pukekohe High School, Sotaro took a particular liking to biology, driven by an innate curiosity about how the body works, particularly the immune system which had given him so much strife in throughout his life.

He went on to study Biomedical Science at Auckland University before undertaking his PhD at the Malaghan Institute supervised by Professors Graham Le Gros and Franca Ronchese, focusing on identifying dendritic cell populations that specialises in priming allergic responses.

“I learned so much in during my PhD, it was an honour to have such renowned immunologists guiding me through the process, ultimately helping me to become a better scientist” says Sotaro. 

Following his PhD, Sotaro went back to Japan for five years to undertake a postdoctoral position at RIKEN, a medical institute in Yokohama.

Here, he conducted research on how itching in skin allergies is triggered by molecules produced by immune cells, which activate sensory nerves.

“Going back to Japan was an incredibly intense experience. Having only lived there as a child, experiencing life as an adult was completely different. I worked a lot of long days where I learned so much.

Sotaro came back to the Malaghan Institute in 2022, bringing back the skills and knowledge from his time away.

“There’s still so much we don’t understand when it comes to allergies, yet the need to know is urgent as the incidence of allergies are increasing every year.”