Adenosine in ambrosia pollen exacerbates allergy

The common ragweed (Ambrosia artemisiifolia) produces pollen which can trigger strong reactions such as asthma. A research team headed by Prof. Claudia Traidl-Hoffmann, who is on the Board of Directors of CK-CARE (Christine Kühne – Center for Allergy Research and Education), has shown that what was previously known as the principal allergen only has such a strong allergenic effect when combined with the substance adenosine, which is also present in the pollen.

The weed Ambrosia artemisiifolia is an invasive plant from North America, which has two challenging characteristics for humans: it is spreading rapidly in Europe – it is also colonising regions in Switzerland – and its pollen has an allergy-promoting effect even in minute quantities. If ambrosia pollen gets into the airways, it induces severe inflammation in the lung tissue. This can produce breathing problems or even asthma. The main trigger in ambrosia pollen was previously thought to be a protein called “Amb a 1”. A lot of people who have come into contact with ambrosia pollen develop antibodies to this substance. This is basically a protective mechanism of the body against unwanted substances or pathogens, but it is initiated in error when a person has an allergy.
However, the protein Amb a 1 is apparently not solely responsible for the inflammatory effect of the ambrosia pollen, as shown by a team led by Prof. Claudia Traidl-Hoffmann, Director of the Institute of Environmental Medicine at the Technical University of Munich (UNIKA-T, TUM) and member of the Board of Directors of CK-CARE (Christine Kühne – Center for Allergy Research and Education): “This only becomes highly allergenic when in combination with adenosine, which is also contained in ambrosia pollen,” states Prof. Claudia Traidl-Hoffman.

The search for the unknown substance
According to the media release from TUM, the researchers studied how different constituents of the pollen acted on lung tissue. The lung tissue was then tested for indicators of inflammation – such as the presence of specific immune cells. The whole pollen extract or the protein Amb a 1 was tested, while at the same time the pollen extract without proteins was also tested. The results were surprising and revealing, as Prof. Traidl-Hoffmann outlines: “Only the whole extract triggered an allergic effect, making it clear that another substance must be causing the allergenic action of the pollen as well as the protein Amb a 1.”
Adenosine was considered as an interesting candidate for substance X. The researchers had already detected it in high concentrations in birch pollen and it is also present in large quantities in ambrosia pollen. They hit the bull’s eye with this theory: once adenosine had been removed from the whole pollen extract, only very slight signs of inflammation occurred. Similarly, if adenosine was administered alone, no pronounced allergic reaction was observed in the lungs. This means: “Only the combination of substances causes an allergic reaction,” concludes Prof. Claudia Traidl-Hoffman.

Will we soon have a possible remedy for allergic asthma?
An interesting aspect is that adenosine is found naturally in the human body. It is involved in lots of processes and nearly all cells carry recognition molecules for adenosine on their surface. So how does adenosine actually intensify an allergic reaction? “Pollen adenosine binds to the endogenous receptors and, in combination with other substances, can trigger allergies”, explains Prof. Claudia Traidl-Hoffman. The research group calls this phenomenon “cross-kingdom signalling”, in which plant messengers bind to human receptors.
The results of the study are also promising with regard to treatment. So-called adenosine receptor antagonists are drugs that can help to treat asthma by blocking the adenosine receptors in the body. Therefore this aspect is also important in terms of research into pollen allergy. “The results show that adenosine plays a key role, especially in the exacerbation of an allergic reaction. This means the inflammatory reaction could be inhibited by blocking the adenosine receptors, where possible”, states the doctor and researcher.

M. Wimmer, F. Alessandrini, S. Gilles, U. Frank, S. Oeder, M. Hauser, J. Ring, F. Ferreira, D. Ernst, J. B. Winkler, P. Schmitt-Kopplin, C. Ohnmacht, H. Behrendt, C. Schmidt-Weber, C. Traidl-Hoffmann, J. Gutermuth, Pollen-derived adenosine is a necessary cofactor for ragweed allergy, Allergy, May 2015.
DOI: 10.1111/all.12642

How flexible are neutrophils to opposing signaling?

Paola Martinez Murillo a postdoctoral researcher in Pierre-Yves Mantel’s group from CK-CARE obtained a Spark grant from the SNSF to investigate the effect of opposite signals on neutrophil biology in atopic dermatitis.

Spark is a Swiss National Science Foundation (SNSF) funding scheme aiming to support projects that show unconventional thinking and introduce a unique approach. The Spark is highly competitive and supports projects based on promising ideas of high originality. CK-CARE was recognized as an eligible institution in June 2023 by the SNSF, opening new funding opportunities for the CK-CARE researchers.

This project aims to understand how two opposing signals: eczema dysregulated immune environment (Th2 response) and bacterial colonization (Th1 response) impact neutrophils function.

Neutrophils are tiny but powerful immune cells in our blood that fight off bacteria and viruses. They live for only 2-3 days and can quickly respond to infections. Neutrophils can adapt to different situations thanks to their genetic instructions (RNA). Our body’s reversible changes in reading DNA, called epigenomic modifications, are crucial for a functional immune response.

Eczema, a chronic skin condition, happens when various factors like genetics, skin damage, and immune reactions go haywire. People with eczema have neutrophils that do not work as well in fighting bacteria, making them more prone to infections.

This study addresses a knowledge gap in neutrophil adaptation to an allergic milieu, by evaluating neutrophil adaptation to anti-bacterial response in a type 2 immune response dominated context such as atopic dermatitis using transcriptional and epigenomic profiling along with comprehensive analysis of neutrophil functionality (netosis, phagocytosis, ROS-production, bactericidal activity, chemotaxis). Building upon in-vitro stimulation insights, then we will aim for a comprehensive analysis of neutrophil functionality in atopic dermatitis patients treated or not with Dupilumab.

Environmental exposure and sensitization patterns in a Swiss alpine pediatric cohort

The level of environmental exposure throughout life may contribute to the prevalence of allergic sensitization and allergic disease. The alpine climate has been considered a healthy climate with little allergen exposure and pollution. We conducted a cross-sectional study to investigate local environmental exposure and concomitant prevalence of allergic sensitization among local school children born and raised in an alpine environment.

Read the full publication

Spatial transcriptomics combined with single-cell RNA-sequencing unravels the complex inflammatory cell network in atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 3%–5% of adults and 20% of children worldwide. The pathophysiology of AD involves various factors including host genetics, altered skin barrier function, and immunological abnormalities. 

Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood

Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls.
An analysis of the CK-CARE-ProRaD cohort revealed adult-onset AD in nearly a quarter of patients. We identified active smoking to be associated with adult-onset AD versus controls. Food allergy, maternal food allergy, palmar hyper linearity, and academic background increased the odds of childhood-onset AD versus controls.

Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis, but reduced odds to feature multiple (3-4) atopic comorbidities. Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in “high-atopic”-clusters.

The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.

Certification by the Swiss Biobanking Platform – VITA-Label

Building up a proper Governance through accountable mechanisms is key to foster trustworthiness and the pre-requisite for the appropriate use of biological resources. Our CK-CARE Biobank has recently been awarded by Swiss Biobanking Platform (SBP) with the VITA Label, which demonstrates compliance with the applicable legal and ethical framework. This labelling approach is part of our long-term strategy to strengthen biobanking practices and provide high-quality samples to the research community.

CK-CARE Team Meeting October 10th- 11th, 2022

This year’s CK-CARE team event in Davos focused on strengthening cross-center communication and collaboration. Our team members got to know each other and the canton of Grisons better by producing several Grisons specialties as “cross-center team building” in preparation for the scientific work. This as a goal to promote teamwork! Although there was no knowledge about the production of Graubünden delicacies, let alone anyone with appropriate skills, each team excelled in its own way. Driven by trust, respect and genuine motivation to solve the tasks set, the team members met the challenge of working together with fun and creativity as an important preparation for the following day’s research activities. It was a successful meeting – we look forward to many more.