Mast cells may play a more central role in the development of asthma than previously demonstrated, according to a the study from the Institute of Environmental Medicine (IMM) at Karolinska Institutet in the publication The Journal of Allergy and Clinical Immunology. The findings may have implications for the development of new asthma treatments.
Asthma is a chronic airway disease affecting millions of people worldwide. People with asthma often have increased numbers of mast cells in their airways, and these cells have long been implicated in the development of the disease. However, the extent to which mast cells contribute directly to the changes occurring in asthmatic airways has remained unclear.
In the new study, the researchers investigated the role of mast cells by inhibiting KIT signaling, which is essential for mast cell survival and function. The experiments were conducted in a clinically relevant house dust mite-induced model of asthma and complemented by experimental studies in human systems.
Inhibition of KIT signaling markedly reduced the accumulation of mast cells in the lungs. It also altered gene activity and reduced the release of mediators that contribute to inflammation and airway constriction.
Most importantly, the treatment prevented several key features of asthma, including bronchoconstriction, airway hyperresponsiveness, inflammation and structural changes in the airways.
“Our findings strengthen the evidence that mast cells are not merely a consequence of inflammation in asthma but can be drivers of the disease process itself. In the longer term, this could contribute to new ways of identifying and treating patients in whom mast cells play a particularly important role”, says Mikael Adner , researcher at the Institute of Environmental Medicine , Karolinska Institutet.
Publication
Selective KIT-inhibition Supports Mast Cells as Key Drivers of Allergic Asthma Pathogenesis.
Xiang Y, Liu J, Atanasoai I, Seren R, Säfholm J, Gong Y, Mogren S, Bosewel CE, Jonsson AK, Samuchiwal SK, Nie M, Höckerlind ER, Andersson C, Wheelock CE, Turner MJ, Nilsson G, Adner M
J Allergy Clin Immunol 2026 Sep;():
