New approaches to the treatment of atopic dermatitis

The epithelium is the outermost layer of cells in an organ and provides a strong barrier function in order to prevent or treat allergic diseases. In the case of an allergy, this cell layer of the skin, nose or lungs becomes permeable. From studies with patients suffering from eczema, asthma or rhinitis, researchers from Area D have learnt that the barrier function of the particular epithelium does not operate properly.

The focus has been placed on tight junctions (TJs). Tight junctions (TJs) are narrow bands of proteins that hold together the outermost cells of a tissue and thereby form a barrier. This prevents penetration by substances from the environment, e.g. allergens, pollutants and bacterial toxins. Defects in the TJs disrupt this barrier function in the airways and lungs therefore play an important role in the development and existence of asthma.
It was suspected that one of the most effective approaches to allergy prevention is to maintain the functionality of these TJs and thereby ensure the tissue does not become permeable.

Early detection of permeability of the epithelium can consequently be used as early diagnosis in allergy-prone children and can help in taking the first necessary precautions. In an initial step, new methods of performing this analysis are being addressed. Thus treatment to protect the barrier function may become the method of choice for some patients with atopic dermatitis or other allergic diseases.

Researchers from Area D have studied the regulation of these TJs by a cell group that is typical of allergies (denTh2 cells) and their released messengers in both healthy and asthmatic individuals. The data showed that these Th2 cells and their messengers reduce the integrity of the TJs and hence the outermost barrier of cells. However, if one specific enzyme (HDAC) has been blocked, the defective barrier function could be restored as the cells increase the formation of TJ molecules.
Four new molecules have been identified which are responsible for the development of eczema in allergy patients. Furthermore, new and promising approaches to the diagnostic criteria and the treatment of the serious form of atopic dermatitis have been defined.

Annual Report CK-CARE 2023

CK-CARE’s work has global resonance and, thanks to this strong position, significant projects in clinical allergy research were again launched or catalysed in the reporting year. CK-CARE’s working methods were sharpened in terms of medical translation and a strengthening of research capacities on the medical campus in Davos was defined in order to increase CK-CARE’s performance.

Annual Report 2023

CK-CARE’s work now has global resonance and, thanks to this strong position, significant projects in clinical allergy research were again launched or catalysed in the reporting year. CK-CARE’s working methods were sharpened in terms of medical translation and a strengthening of research capacities on the medical campus in Davos was defined in order to increase CK-CARE’s performance.

Kühne-Foundation Annual Report 2023

“Entrepreneurial success should go hand in hand with the promotion of  the common good. The Kühne Foundation fulfills this task. With a variety of programs and projects, the founder and the Kühne Foundation also assume their socio-political responsibility.”

The activities were significantly expanded, particularly in the area of logistics. In addition, the new focus area of climate action was established, and the first projects were launched.

Prof. Dr. h.c. Klaus-Michael Kühne

 

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.

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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.