PhD defence Ms C.S. (Carli) Koster

Asthma has nerves: unravelling mast cell-sensory neuron partnerships in neuroplasticity

Asthma is a chronic inflammatory disease of the airways that causes shortness of breath, wheezing, and coughing. Besides the immune system, which causes the inflammation of the airways, the nervous system also plays an important role in asthma. As nerves in the airways can become overly sensitive and undergo structural changes, a process known as neuroplasticity. This thesis investigated how interactions between nerve cells and immune cells contribute to these neuroplasticity changes in asthma.

In lung tissue from patients who died from severe asthma, we observed an increased number of nerve fibres and immune cells surrounding these nerves compared to healthy lung tissue. These findings suggest that changes in the airway nerves are a characteristic feature of severe asthma. To further study these mechanisms, we developed a human cell model of sensory neurons derived from stem cells. Using this model, we showed that asthma associated inflammatory factors can directly alter both the structure and sensitivity of sensory nerves. In particular, the inflammatory factor TGF-β caused changes in nerve responsiveness and neuronal networks. We also investigated direct interactions between sensory nerves and mast cells, a type of immune cell that plays a central role in allergic inflammation in asthma. These interactions mainly enhanced inflammatory responses in mast cells, while having limited effects on nerve structure and function.

Overall, this thesis demonstrates that communication between the immune and nervous systems contributes to asthma-related changes in the airways. The newly developed human models provide valuable tools for studying asthma and may support the development of new treatment strategies.

Supervisors:prof. dr. R. (Reinoud) Gosens, prof. dr. B.N. (Barbro) Melgert
Co-supervisor:M. (Mihály) Balogh, PhD