Marking of the different mast cell populations (in green and red), which are major players in allergic responses, on contact with neurons (white) in mouse skin. © Dr. Marie Tauber and Dr. Lilian Basso.

Allergic diseases affect up to one third of the world’s population, and their prevalence is on the increase. In order to develop more targeted and effective therapies, research is mobilizing to better understand the biological and cell mechanisms involved in the onset of allergies. Mast cells – a type of immune cell – is of particular interest to scientists and doctors, but there is little data about them at present. In a new study published in Journal of Experimental Medicine in July 2023, researchers from Inserm, CNRS and Université Toulouse III – Paul-Sabatier, at the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), broadened our understanding of these cells and created the first digital mapping of mast cells in humans. These findings open up avenues for the adaptation of therapeutic strategies.

Allergic diseases are a major public health problem, to the extent that the World Health Organization (WHO) has classified allergy as being the world’s fourth leading chronic disease. It is currently estimated that 25 to 30% of the population suffers from an allergy, be it food, skin or respiratory allergy, and this proportion could increase to 50% by 2050. A better understanding of the underlying biological mechanisms is a key step if we are to develop more targeted and effective therapies.

This is the goal of Inserm researcher Nicolas Gaudenzio and his team at the Toulouse Institute for Infectious and Inflammatory Diseases. In 2019, the scientists had published a first article in Nature Immunology, showing the crucial role played by immune cells known as “mast cells” in the initiation of eczema. This research has given rise to new therapies that are currently in development.

Mast cells remain poorly understood by scientists. We know that their functions go far beyond problems of allergies and that they can have roles that are either beneficial (such as in fighting bacteria) or not, depending on the pathology. Research has also led to their classification into two large families of mast cells: the CTMCs found mainly in the skin and the MMCs located mainly in the gut mucosa.

However, much remains to be learned about these cells that are complex to study, especially because it is difficult to extract them from tissue.

“If we are to understand how we can act on mast cells and block their harmful action in terms of allergic diseases, we need to improve our knowledge of these cells. This involves determining their location, if there are several types beyond the dichotomy which has traditionally been described, and whether their functions differ according to the tissues in which they are located,” points out Gaudenzio.

In this new study, the research team used more recent technologies to study mast cells more precisely in mice and humans. The scientists used the single-cell sequencing technique: they sequenced the RNA of individual cells from several organs in order to extract their individual “identity card”.

Analyzing human cells with this method reveals a much more complex image than has hitherto been described. Indeed, the cells of over thirty human organs were analyzed thanks to advanced techniques for exploring data banks and bioinformatics. The researchers thus identified not two but seven different subtypes of mast cells, with various characteristics and functions.

From this data, the team was able to create and enable open access to the first “digital mapping” of human mast cells, which allows any scientist to see at a glance which mast cell subtype is associated with which organ and learn more about its function.

This diagram shows, in a simplified way, the distribution of the different mast cell subtypes through different organs of the body.

This approach represents a major paradigm shift since the new mapping makes it possible, just by querying a database, to better understand the natural diversity of mast cells in allergic diseases, and thus open up a process of reflection on the need to adapt therapies to more precisely target the cell subtypes involved.

“This study is the first foundation stone of a vast building that is expected to transform the anti-allergy therapies and move towards a greater personalization of treatments, with more efficacy and fewer side effects. We will continue to supplement this mapping by studying mast cells in different disease settings, in treated and untreated patients alike, so that it is as precise as possible for the scientific and medical community that is working on allergies,” concludes Gaudenzio.  

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