PhD defence G. (Guilherme) Dragunas

Stressing the airways: neuronal plasticity in allergic airway inflammation

Guilherme Dragunas has elucidated key mechanisms of neuroplasticity in asthma, paving the way for novel anti-asthma drugs. Dragunas: 'Airway neurons carry multiple functions in the lungs, ranging from breathing regulation to sensing inhaled noxious particles. In asthma, it appears that these neurons function aberrantly due to being changed after a long period of inflammation, a process called neuroplasticity. Despite advancements in therapy, subsets of patients remain not well controlled. Understanding how neuroplasticity occurs in the asthmatic airways can yield novel druggable targets. Multiple factors can influence this process, such as circulating hormones, such as the ones found in psychological stress exposure, and immune cell-nerve interaction. Thus, we focused on the mechanisms governing neuroplasticity in asthma and associated modulators to understand better the disease pathophysiology and possible intervention opportunities.

In human bronchial samples, we observed that asthma presented an increased area of cholinergic innervation. This branching and associated airway hyperresponsiveness were inhibited when a growth factor pathway called BDNF/TrkB signalling was inhibited in mice. Using a model of airway cholinergic neuron differentiation from stem cells, we have found that the glucocorticosteroid dexamethasone, a class of drugs widely prescribed for asthma and lung maturation, can induce changes in the functionality and differentiation of these neurons. In samples of patients with fatal asthma, we observed an increased innervation area surrounding the airways correlated to increased inflammatory cells surrounding nerve bundles. Finally, we have observed that chronic, but not acute, stress can potentiate inflammation in mice submitted to allergic lung inflammation and modulate neurotrophic factors’ expression in the lungs.'

Promotors: Prof.dr. R. Gosens