Identification of new effector B cell subgroups and their role in allergic diseases

05. May 2016

B cells play an important role in the human immune system because they are the cells that produce antibodies. A research team at SIAF led by Professor Cezmi Akdis (Workpackage 2) recently reported that B cells – apart from their role antibody-producing cells – can function as regulators of the immune response by the production of cytokines. Certain subgroups of B cells were identified which produce specific cytokines. For instance, regulatory B cells produce the anti-inflammatory cytokine interleukin-10 and are hence able to protect against autoimmune diseases and allergic inflammation.

The aim of this study is to identify new human cytokine-producing B cell subgroups and research their role in immune regulation. B cells cannot be cultured for lengthy periods in vitro. Therefore we suppressed the cell division of the B cells by increasing the production of two specific genes (BCL-6 and BCL-xL). The method of suppressing cell division and increasing the production of certain proteins is known as over-expression. This makes it possible for us to form long-lived B cells. To enable us to characterise individual B cells, we isolated individual cells and generated B cell clones. Then we studied the gene activity of these clones in detail by means of next-generation sequencing (determining the nucleotide sequence of the RNA).

To allow us to identify new effector B cell subtypes that produce specific cytokines, we had to group the individual B cell clones based on their cytokine expression. Using this approach we identified 6 clone groups which expressed specific cytokine profiles, i.e. activated specific cytokines. Some of these cytokine profiles (an expression profile shows what the cell actually does) resembled previously described subgroups of effector B cells, such as the interferon-gamma-producing B cells and the interleukin-10-producing regulatory B cells. Interferon is a protein that exerts an immunostimulating, primarily antiviral effect; interleukin is a cytokine with an anti-inflammatory effect, which inhibits the inflammatory reactions taking place in the body. In addition, we found other clusters with different cytokine profiles, which have not previously been described. At present we are working on carrying out detailed characterisation of these new B cell subgroups so that their potential role in allergic diseases can be assessed.

How flexible are neutrophils to opposing signaling?

22. February 2024

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

19. December 2023

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

6. September 2023

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

14. June 2023

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

7. November 2022

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

17. October 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.