New insights into the mechanisms of allergic inflammation

Allergic diseases have become more common in recent decades, especially in developed industrialised countries. For example, the number of people suffering from allergic asthma is constantly increasing. In 2019, nearly 300,000 people were eligible for special prescription asthma medicines in Finland.

Despite their ubiquity, the molecular mechanisms of allergic inflammation are still partly unknown. A lot of basic research is being done in this area, for example to develop new medicines.

The body's own inflammatory mediators, cytokines, are known to play an important role in allergic inflammation. A key cytokine that maintains allergic inflammation is interleukin 13 (IL-13). In allergic asthma, for example, IL-13 causes, contraction of the smooth muscle cells in lungs which results in bronchoconstriction and shortness of breath.

An important cell type that produces IL-13 in allergic inflammation is the mast cell. These cells are widely distributed in different tissues of the body, especially in the skin and mucous membranes, where they come into contact with external pathogens and allergens. IL-13 is thought to have a broad effect on the cells of the body's immune defence system, but there has been no information on its effects on mast cells.

In a study on mice, the researchers found that the mast cells do not express the IL-13 cytokine receptor at all and therefore do not respond to the IL-13 cytokine present in their environment.

“In mice, only T cells have previously been thought to be negative for the IL-13 receptor. We have now shown that mouse mast cells are surprisingly similar to T cells in this respect, i.e. they are negative for the IL-13 receptor. In striking contrast, closely related basophils or macrophages responded well to IL-13 cytokine,” says Professor Ilkka Junttila. “The lack of the IL-13 receptor in mast cells causes their inability to respond to cytokine, i.e. these cells are unable to detect the cytokine, which they themselves produce in high levels during allergic inflammation.”

According to the researchers, it will be important in the future to find out whether human mast cells function in the same way and whether the expression of the IL-13 receptor in mast cells is altered in diseases such as allergic asthma or atopic dermatitis or the rarer mast cell-related diseases, such as mastocytosis, which causes varying degrees of skin changes.

The finding means that treatments targeting the IL-13 cytokine, such as monoclonal antibodies, are unlikely to affect mast cell function. “There is a feverish search for new effective treatments for allergies. Antibodies that neutralise IL-13 cytokine are also in clinical use. If future studies confirm that the mast cells of allergic individuals are negative for the IL-13 receptor, it is clear that the mast cells are not affected by this treatment. This could shed light on why IL-13 neutralising therapy has been somewhat disappointing in clinical efficacy,” Junttila says.

The study was recently published in the Journal of Leukocyte Biology. It has been funded by the Academy of Finland, Tampere Tuberculosis Foundation, NordLab project funding, PSHP VTR funding, Orion Research Foundation and Allergy Research Foundation.

Research publication: Tanja Salomaa et al., Low IL-13Rα1 Expression on Mast Cells Tunes Them Unresponsive to IL-13, Journal of Leukocyte Biology, 2023;, qiad065, .org/10.1093/jleuko/qiad065

Ilkka Junttila is Professor of Clinical Microbiology at the University of Oulu, Chief Medical officer of Clinical Microbiology at NordLab Welfare Group and University Researcher at the Tampere University.