09:20am Monday 13 July 2020

New insights in the interplay between dendritic cells and epithelial cells in asthma

There is an epidemic of asthma in the Western world, of which the cause in unclear, and for which novel forms of prevention and treatment are urgently needed. Bart Lambrecht and Hamida Hammad (VIB Department for Molecular Biomedical Research, UGent) study the role of lung dendritic cells in asthma, with as ultimate goal finding novel treatment strategies.

Not all dendritic cells (DC) of the lung have the same role in asthma.

You unraveled how labor is divided between two subsets of DC. Can you elaborate?

Hamida: For a long time, the DC was considered as a single cell, distinct from macrophages, in that it excelled in presenting antigens to naïve T cells and thus initiated the immune response.  We now realize that these cells come at least in three flavors. Some DCs specialize in presenting antigens from virally infected epithelial cells to CD8+ cytotoxic T lymphocytes (a process called cross-presentation), some specialize in presentation of soluble antigens and allergens to CD4+ T helper lymphocytes. We also realize now that some DCs are in fact close relatives of macrophages. What the new study in Immunity is showing is that CD11b+ DCs cause allergy to develop, whereas the macrophage-like DCs orchestrate the allergic response and recruit eosinophils to the lungs of asthmatic mice. Both subsets could be therapeutic targets for novel forms of anti-inflammatory drugs.

You use different markers to recognize different DCs. Do these markers have a potential for purposes other than research?
We have found that the same set of markers is also expressed by human DC subsets. There might be diagnostic applications for patients, and we might one day target antigens to particular DC subsets for immunotherapy of allergy, infectious disease or cancer.

You work in mice, are there initiatives to translate this to the clinic?
We have access to clinical bronchoscopy and sputum samples of asthma patients seen in UZ Gent. We are planning a study to see if house-dust mite allergic asthmatic patients have the same basic setup of DC subsets compared with healthy controls. Our research is always centered on clinical questions, and studying the in-depth mechanisms of why people become sensitized to allergens will maybe one day translate to new intervention strategies. In this regard, we are also studying the influence of common causes of allergy like air pollution and cigarette smoking on the function of DCs and development of allergy in the mouse.

Together you recently received the Karel Lodewijck Verleysen award of the Royal Society of Medicine of Belgium (60,000 €) for your research. What does this mean for you? 
In the first place, it means appreciation of our work. We will also receive some research budget to study the influence of epithelial cells on lung DCs in allergic asthma.

As a woman it is not always easy to pursue a scientific career. You are a successful scientist, why do you find it important to take up this challenge? 
For me, research is fun in the first place. When I dig into a problem, I really want to know what is happening. Sometimes this takes us to areas of the immune system where we have never worked before, and our lab is not afraid to tackle these new problems. It is nice to come to work and have the impression in the evening that you have learned something. This is science for me, and I couldn’t live without it.

Plantinga et al., Immunity 2013There is an epidemic of asthma in the Western world, of which the cause in unclear, and for which novel forms of prevention and treatment are urgently needed. Bart Lambrecht and Hamida Hammad (VIB Department for Molecular Biomedical Research, UGent) study the role of lung dendritic cells in asthma, with as ultimate goal finding novel treatment strategies.

Not all dendritic cells (DC) of the lung have the same role in asthma.

You unraveled how labor is divided between two subsets of DC. Can you elaborate?

Hamida: For a long time, the DC was considered as a single cell, distinct from macrophages, in that it excelled in presenting antigens to naïve T cells and thus initiated the immune response.  We now realize that these cells come at least in three flavors. Some DCs specialize in presenting antigens from virally infected epithelial cells to CD8+ cytotoxic T lymphocytes (a process called cross-presentation), some specialize in presentation of soluble antigens and allergens to CD4+ T helper lymphocytes. We also realize now that some DCs are in fact close relatives of macrophages. What the new study in Immunity is showing is that CD11b+ DCs cause allergy to develop, whereas the macrophage-like DCs orchestrate the allergic response and recruit eosinophils to the lungs of asthmatic mice. Both subsets could be therapeutic targets for novel forms of anti-inflammatory drugs.

You use different markers to recognize different DCs. Do these markers have a potential for purposes other than research?
We have found that the same set of markers is also expressed by human DC subsets. There might be diagnostic applications for patients, and we might one day target antigens to particular DC subsets for immunotherapy of allergy, infectious disease or cancer.

You work in mice, are there initiatives to translate this to the clinic?
We have access to clinical bronchoscopy and sputum samples of asthma patients seen in UZ Gent. We are planning a study to see if house-dust mite allergic asthmatic patients have the same basic setup of DC subsets compared with healthy controls. Our research is always centered on clinical questions, and studying the in-depth mechanisms of why people become sensitized to allergens will maybe one day translate to new intervention strategies. In this regard, we are also studying the influence of common causes of allergy like air pollution and cigarette smoking on the function of DCs and development of allergy in the mouse.

Together you recently received the Karel Lodewijck Verleysen award of the Royal Society of Medicine of Belgium (60,000 €) for your research. What does this mean for you? 
In the first place, it means appreciation of our work. We will also receive some research budget to study the influence of epithelial cells on lung DCs in allergic asthma.

As a woman it is not always easy to pursue a scientific career. You are a successful scientist, why do you find it important to take up this challenge? 
For me, research is fun in the first place. When I dig into a problem, I really want to know what is happening. Sometimes this takes us to areas of the immune system where we have never worked before, and our lab is not afraid to tackle these new problems. It is nice to come to work and have the impression in the evening that you have learned something. This is science for me, and I couldn’t live without it.

Plantinga et al., Immunity 2013
VIB

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