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In Focus: Surveillance cells in the skin and their role in allergy

12 July 2023

Evelyn Hyde is a senior research officer who is taking a deep dive into the specific cells and molecules involved in the development of allergies, bringing us closer to a future where allergies can be better understood and managed.

Evelyn joined the Malaghan Institute in 2005 and has been part of the Ronchese Laboratory since 2009. Her work focuses on understanding the early stages of allergy development, particularly the role of dendritic cells, a type of immune cell.

“Dendritic cells collect molecules that the body is exposed to and present them to other parts of the immune system,” says Evelyn.

“The dendritic cell is thought to teach a part of the immune system called T-cells whether the fragments it collects are a threat or not and instruct T-cells on the specific type of response that should be mounted if those fragments are encountered again in the future.”

“The skin is effectively the starting point for allergic responses.”

Evelyn's research is trying to decipher the signals received by dendritic cells to understand the immune responses they trigger and how this might lead to allergies.

In 2020, the Ronchese lab made a seminal discovery, finding that the skin is a special organ when it come to the development of allergic responses. 

The skin is one of the most vulnerable parts of the body. It is our first line of defence and at a microscopic level, it is like a dry, hostile desert with an endless horizon of dead skin cells.

Several million times a day, debris of all shapes and sizes rains down onto the skin’s surface from our environment. The skin also receives various alien visitations: some of them are friendly, harmless critters, while other germs are there to invade the body.

One of the inhabitants of this hostile wasteland are dendritic cells who have been tasked with an ongoing reconnaissance mission to survey the area and alert the T-cells in the body if they detect a threat.

Once the dendritic cells signal that a particular substance is a threat, it can be remembered by the body for life. If the body is exposed again to this reported threat, a full-scale immune response may automatically be launched to defend the body.

“In theory, this should help produce a faster response upon re-exposure to any of the threats that our body faces every minute of every day,” says Evelyn. 

But dendritic cells can falsely perceive threats in mundane, harmless substances, sending out a danger signal to the body. This is one way that allergies develop.

“We're hoping it will bring us one step closer to understanding how allergies develop because honestly, it is an area we know relatively little about.”

The Ronchese lab found that in mice, the skin produces a molecule called IL-13 which increases the sensitivity of these dendritic cells to induce allergic responses.

“Previously, IL-13 was thought to be released as a result of exposure to an allergen or due to infection. However, our research shows that even in healthy individuals, IL-13 is always present in the skin, programming the immune system to produce allergic responses.” says Evelyn.

“This suggests that the skin is effectively the starting point for allergic responses.” 

The lab is now developing methodologies to investigate how human dendritic cells in the skin respond to IL-13 and if this is comparable to mouse models.

“We are currently investigating how to extract dendritic cells from the skin of human participants.”

They are trialling a method which uses a suction cup on the surface of the skin to create a fluid-filled blister from which the fluid is then extracted.

“I know it sounds a bit disgusting, but it’s proved to be a good way to extract dendritic cells from the skin and it’s close to painless,” says Evelyn. 

“We're hoping it will bring us one step closer to understanding how allergies develop because honestly, it is an area we know relatively little about.”

By investigating how human dendritic cells respond to IL-13, the Ronchese lab aims to bridge the gap between mouse models and human immunology, advancing our knowledge of allergy development and potentially leading to improved treatment and prevention strategies.

Evelyn was first captivated by immunology when she was studying at the University of Otago.

“Immunology is connected to everything. Whether it’s related to good health or bad health, our immune system is always involved,” she says.

“Nothing is ever black and white in immunology. It’s about careful balancing of so many different moving parts.” 

Evelyn does her own balancing act as she juggles her scientific work and personal life. Recently, she has started playing the cello again. 

“I used to play as a child and up until about ten years ago, but have played a lot less as life got busy,” says Evelyn.

“I’ve recently picked it back up and joined the Wellington City Orchestra for some fun.”

Playing the cello serves as a creative outlet and a means to recharge her spirit.

“Research can be difficult at times. I love the fact that no one day is the same and you just don’t know what to expect but it takes a lot of perseverance.”