Duplicitous basophils and atopic disease
Basophils are an odd type of cell. There’s not much we know about them, partly because they’re one of the rarest types of immune cell, but they crop up again and again in allergy disease research – which hints they may play an important role. However, which role do they play? Do they help, or hinder the immune system?
A recent publication in the Journal of Allergic and Clinical Immunology suggests they do both; simultaneously contributing to dangerous inflammation in the skin while working to suppress that same inflammation. The results, while contradictory, highlight the importance of these poorly-understood cells and their potential significance in emerging immunotherapies.
“Basophils are a type of immune cell that circulate in your blood stream,” explains Dr Pellefigues who led this study with the Malaghan Institute of Medical Research’s asthma, allergy and parasitic disease research team. “They’re quite rare, and are among a group of cells called ‘granulocytes’ – cells that contain granules. You can stain these granules with different dyes to see them down a microscope. Basophils get their name because the dyes used to see them are ‘basic’.
“We wanted to understand the precise role of basophils during atopic dermatitis. Our research shows that basophils are specifically causing problems with the epidermis during atopic inflammation, which leads to a dysfunction of the epidermal barrier. This is really important as this dysfunction is known to cause atopic disease, independently of any other factors.
“But, while trying to unravel the mechanisms by which basophils contribute to inflammatory disease, we unexpectedly found that basophils also help reduce inflammation, by inducing the expansion and function of ‘anti-inflammatory’ M2 macrophages – another kind of immune cell.”
So while on one hand, basophils are implicated in weakening the barriers in the skin, with the resulting inflammation leading to the development of atopic disease, on the other, they also help suppress inflammation in the same area. These findings are important in the context of emerging immunotherapies, which often suppress the immune cells that contribute to inflammation. That may not be the wisest thing, in the case of basophils, because of their contribution to reducing inflammation too.
Dr Pellefigues gives the example of dupilumab – an emerging ‘miracle drug’ which is used to treat atopic dermatitis patients by blocking the IL-4 receptor. “We don’t yet know exactly how it works. But as we show that IL-4 (secreted by basophils) has both deleterious and beneficial roles in the atopic skin, there is still room for improvement towards more specific immunotherapies"
“These results suggest that targeting basophils may also inhibit some natural anti-inflammatory mechanisms. Understanding how to dampen only atopic inflammation but not natural anti-inflammatory pathways could lead to new improved targeted immunotherapies, with less side effects, and greater benefits for the patients.
“Fundamentally, this paper leads the way to further research into anti-inflammatory roles of basophils. This may be the tip of the iceberg, and prove to be the main function of these very rare cells,” Dr Pellefigues says.
“Clinically, this will help pharmaceutical companies develop new, better targeted immunotherapies, with less side effects, to treat atopic dermatitis, which is major morbidity burden in the industrial word, affecting up to 30% of people, mainly during early infancy.”