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Immune system discovery could lead to better treatments and vaccines

10 November 2020

New findings about how the immune system responds to threats is taking us one step closer to more targeted treatments for allergies and autoimmune disorders and more effective vaccines.

Professor Franca Ronchese (left) and Dr Kerry Hilligan

Health Research Council of New Zealand-funded research by the Malaghan Institute, published in Nature Communications, reveals that the same subset of immune cells – dendritic cells found on the skin – can start different types of immune responses depending on the conditions they are exposed to. It was previously thought that different populations of dendritic cells were responsible for initiating different immune responses in the body.

“We wanted to better understand how different types of immune response start – something that scientists have been researching for decades,” says the Malaghan Institute’s Professor Franca Ronchese.

“Parasites, allergens, other pathogens – they all elicit a distinct response. We know roughly what kinds of immune cells are involved in the response, but how they get going, how they arrange themselves, and how they respond to different stimuli is worth investigating given the implications for vaccine design and for redirecting immune responses when they go rogue or overreact.

“What we found is that one specific type of skin dendritic cell – the dermal IRF4+ dendritic cell – is responsible for driving the various types of immune response in the body, rather than different populations of dendritic cell. These ‘elite’ dendritic cells have receptors that recognise the type of microbe that is invading. They use this information to inform the rest of the immune system what the appropriate response should be. If something goes wrong, as is the case with allergies, it’s likely that it’s these elite dendritic cells misinforming the immune system.”

Prof Ronchese says the new knowledge could ultimately enable gentler, more targeted therapies for diseases caused by an over-reaction of the immune system.

“Currently, many treatments – such as steroids – work by eliminating cells in the immune system that are driving the allergic response. While they reduce harmful inflammation, they often do so at the expense of the good inflammation that protects us from infections. With greater understanding of the molecular changes that occur within these specific dendritic cells we could reprogramme them to prevent them from driving the allergic response.”

She says the findings also have implications for vaccine design.

“Designing a good vaccine means targeting the type of cells that start the immune response that kills the infection or the pathogen,” says Prof Ronchese. “So understanding which cells drive the response is essential. Our results are showing that these specific dendritic cells have a much larger role to play than previously thought, which could usefully inform vaccine design.”

View the paper 'Dermal IRF4+ dendritic cells and monocytes license CD4+ T helper cells to distinct cytokine profiles'