The study in mice, recently published in the Scientific Reports Journal, highlights the promising role of Breg cells—specialised immune cells known as regulatory B cells—in treating atopic diseases (AD).

These cells produce interleukin-10 (IL-10), a powerful anti-inflammatory molecule that helps control excessive immune responses. The research specifically explored how these IL-10-producing Breg cells can suppress the activation and infiltration of eosinophils, which are white blood cells involved in allergic reactions and inflammation, into tissues. 

Introduction

Atopic dermatitis (AD) is a chronic inflammatory skin condition that significantly impacts quality of life. The symptoms are itching, eczema, and dryness, and they arise from a complex interplay of genetic predisposition and environmental factors. 

AD has a high prevalence in childhood and poses significant challenges because its underlying causes are not fully understood.

Around 15–30% of children and 2–10% of adults worldwide live with AD. 

Treatments like avoiding allergens and using corticosteroids face challenges in achieving remission because they may not work well for everyone and can have side effects.

A key feature of AD is eosinophilia, which refers to an elevated number of eosinophils—white blood cells that are typically involved in allergic reactions and inflammation.

These cells are believed to play a critical role in the development and worsening of AD. Regulatory B cells (Breg cells), which produce interleukin-10 (IL-10), have shown potential in counteracting the inflammation associated with AD. Their ability to reduce excessive immune responses may offer new avenues for therapy in managing this complex condition.

Methods

This study conducted a series of experiments to investigate how IL-10-producing regulatory B (Breg) cells can reduce symptoms of AD by inhibiting the activation and infiltration of eosinophils into the skin. The research included laboratory (in vitro) and animal-based experiments.

To explore how eosinophils contribute to AD, the researchers used a special type of genetically modified mice called IL-5Rα-deficient (Il5ra−/−) mice.

These mice lack the IL-5 receptor alpha chain, which is essential for the development and function of eosinophils, meaning they do not have functional eosinophils.

Researchers used MC903, a vitamin D3 analogue, to replicate AD symptoms in mice.

Results

When AD was induced in Il5ra−/− mice, they exhibited much milder symptoms compared to normal mice, highlighting the crucial role that eosinophils play in the development and severity of AD.

When purified regulatory B (Breg) cells were introduced into mice with AD, the severity of the disease was greatly reduced.

Further investigation showed that this beneficial effect was due to IL-10, an anti-inflammatory cytokine produced by the Breg cells. IL-10 directly prevented eosinophils, which are immune cells involved in allergic inflammation, from becoming activated and moving into the skin, thereby reducing the inflammation and symptoms associated with AD.

In laboratory (in vitro) experiments, it was further demonstrated that Breg cells were able to reduce the secretion of eosinophil peroxidase, a harmful enzyme released by eosinophils during inflammation.

This inhibitory effect was found to rely on IL-10, meaning that the presence of IL-10 was essential for Breg cells to suppress the eosinophil activity.

The study's findings collectively show that IL-10 produced by Breg cells helps alleviate AD by preventing eosinophils from activating and infiltrating tissues. This study uncovers a new regulatory mechanism involving Breg cells, which could serve as a basis for developing new Breg-based therapies to treat AD in the future.

Conclusion

This study confirms that activated eosinophils play a crucial role in the development and severity of atopic dermatitis (AD). Through the secretion of IL-10, Breg cells effectively reduce AD symptoms by preventing eosinophils from infiltrating lymph nodes and skin and by inhibiting their activation and release of inflammatory substances like eosinophil peroxidase (EPO).

However, since eosinophils are not the sole contributors to AD, relying solely on Breg cells for treatment may have limitations. Therefore, enhancing the function of other immune-regulatory cells, such as regulatory T cells, alongside Breg cells, could offer a more comprehensive and sustainable approach to treating AD.

What are the important implications of this study for people with Eosinophilic-Associated Diseases?

People with Eosinophilic-Associated diseases (EADs) often have a history of atopic conditions like dermatitis (eczema), either personally or within their families. According to our internal survey (2021), 80% of our community members report having some form of atopic disease.

Currently, there is a lack of personalised treatment options for these conditions. This research offers potential new management strategies for those with eosinophil-driven diseases.

The study shows that IL-10-producing regulatory B (Breg) cells can reduce eosinophil activity and tissue infiltration. It suggests that therapies aimed at enhancing Breg cell function or IL-10 production could possibly effectively treat AD.

Such targeted treatments could provide more precise and personalised care than the available broad-spectrum therapies.

Read the full study