A new treatment for allergies

07. July 2015

Scientists from the Swiss Institute of Allergy and Asthma Research (SIAF) in Davos, from the University of Tokyo, the RIKEN Research Institute in Yokohoma, and from Stanford University recently discovered mechanism that stops the body from reacting with an excessive immune reaction. This could be the basis for a new way to handle allergies.

Most people with allergies have to take medication throughout their life: Their body “thinks” that proteins from the environment are so “strange” that they elicit an immune reaction. Until present, it was not possible to develop an efficient therapy so that the body “learns” to stop in an overreacting way.

Mast cells play a key role in the disease process in allergies: As a reaction towards an allergen – for example pollen or dust mites – they release big amounts of substances that initiate an inflammatory process. Study leader Hideaki Morita and his team discovered that mast cells are not only “bad guys”, but also have a “good side” (see figure): They release the substance interleukin-2 that induces the production of certain immune cells called T-regulatory (Treg) cells. Treg cells can suppress the allergic inflammatory process in the airways induced by interleukin-10.
It is already known for some time that Treg cells can subdue an excessive immune response and the resulting inflammation. For example, injections with Treg cells prevented autoimmune diseases in mice. However, for Treg cell treatments one needs a large amount of these cells, which is not easy to realise. In the blood, there are just a few of them, and in vitro they are difficult to produce. Using mast cells, Treg cells could be easily produced in the laboratory in large quantities. “The mechanism that we discovered, could be the basis for a new way to handle allergies,” says Hideaki Morita.

Felicitas Witte

Source:
Morita et al., An interleukin-33-Mast Cell-interleukin-2 Axis Suppresses Allergic Inflammation Induced by Papain-Promoting Regulatory T Cell Numbers, Immunity (2015), http://dx.doi.org/10.1016/j.immuni .2015.06.021

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.

Read the full publication

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.