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Allergy Today Expert article

Dendritic cells and the allergic response

The Malaghan Institute of Medical Research’s Professor Franca Ronchese is working on preventing dendritic cells from causing harmful allergic reactions – without stopping them doing their important job of keeping us healthy.

ATe Dec18 Malaghan - image-849While all immune cells have an important role in maintaining a healthy immune system, some cells play a more active role than others. This makes them of great interest to scientists who wish to understand how and why immune reactions take place.

Depending on the context, immune responses can be both ‘good’ (protecting the body against threats) and ‘bad’ (responding negatively to something that should be harmless). The latter includes allergic reactions, which can range from an inconvenience to a life-threatening anaphylactic attack.

Among these active immune cells that interest researchers such as Professor Franca Ronchese of the Malaghan Institute of Medical Research are dendritic cells. Dendritic cells act like sentinels of the immune system – patrolling the body and priming immune responses – including allergic reactions. Because of this, Prof Ronchese and her immune cell biology team are working hard to get to the bottom of what dendritic cells are and how they operate.

The life of a dendritic cell

Starting their short life in the bone marrow, dendritic cells quickly leave their home and travel around the body. They settle into places like the skin, the gut, the bloodstream and the airways. Once there, they probe their surroundings for information, looking for signs of trouble. If they find it, they take that information to the central command of the immune system, the lymph nodes, which decide on how to appropriately respond to this threat.

“Take dendritic cells in the skin, for example,” says Prof Ronchese. “If you get stung by a bee or cut yourself, there’s a breach where something foreign is getting in, like venom or bacteria.

“Dendritic cells take up samples of those foreign materials and present them to the cells inside the lymph nodes. The cells in the lymph node then send signals about how to deal with this invasion and protect the body from this threat.”

Once dendritic cells have finished informing lymph nodes about the environment, they die. The whole process takes about a week, with new cells produced to take their place and protect the body.

A key role in allergies

While dendritic cells are vitally important, acting as the eyes and ears of the immune system, they don’t always get it right.

Sometimes dendritic cells take something perfectly harmless, such as a peanut molecule, and present it to the immune system as something harmful. In some cases, this mishandling can severely exacerbate the way our body responds to allergens.

“New research published in the prestigious journal Science shows that dendritic cells can directly pass on food allergens from the blood to inflammatory mast cells in the skin. This process can trigger anaphylaxis in individuals who are sensitive to that particular allergen,” says Prof Ronchese.

“The study showed that when dendritic cells were removed, no anaphylaxis took place. So not only can dendritic cells prime allergic responses, they can contribute to their severity too.”

While it’s possible to remove dendritic cells from the body with steroids, Prof Ronchese explains that’s hardly a practical solution to deal with allergies.

“Steroids don’t just kill one immune cell, they wipe out a plethora of immune cells in the body, which means we’re defenceless from infection until new cells are made. Rather than wiping out dendritic cells, we need to find ways to interrupt their harmful processes.”

Looking under the hood

Finding ways to prevent dendritic cells from causing harmful allergic reactions is a wide topic of research. However, while there’s a good deal of understanding of what dendritic cells do and where they do it, their inner workings remain largely a mystery.

“It’s like trying to fix a car engine without looking under the hood,” explains Prof Ronchese.

“We know how a car runs, where the parts are, but we can’t fix the problem without getting a look inside.”

To get under the hood of dendritic cells, Prof Ronchese’s team are looking at their DNA. The team is investigating which parts of their DNA are turned on and off when they’re exposed to different types of allergens.

The process generates huge amounts of data about dendritic cells. By laboriously sifting through it and honing in on the genes that control the allergic reaction, the team can use this knowledge to pinpoint where and how they can interrupt dendritic cells – without stopping them from doing their important job of keeping us healthy.

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Professor Franca Ronchese is the immune cell biology programme leader at the Malaghan Institute of Medical Research.

December 2018