Influence du facteur neurotrophique Neurturine dans les cellules nerveuses et immunitaires lors de l’inflammation des voies respiratoires. (Doctoral thesis)

Allergic asthma is a chronic inflammatory disease in response to allergens and environmental irritants. The pathophysiology of asthma is defined by airway inflammation and airway hyperreactivity. Interestingly, it has been shown that there is a link between neurogenic and immune airway inflammation. Moreover studies suggest that neurotrophic factors participate in the pathogenesis of many features and symptoms of asthma.Neurturin (NTN) is a neurotrophic factor which could be involved in the modulation of many symptoms of asthma through the GDNF family receptor alpha 2 (GFRalpha2) and the proto-oncogene RET co-receptor. However, the underlying mechanisms remain unclear. By studying WT and NTN-/- mice after acute and chronic airway inflammation protocols induced by the allergens ovalbumin or house dust mite, we investigated how NTN is able to modulate the level of Th2 responses through neurogenic inflammation and immune cells’ regulation. We analysed its relationship with structural airway remodelling and we also tested the potential anti-inflammatory role of NTN in vitro.The achievements suggest that Neurturin acts in vivo and in vitro as an anti-inflammatory mediator.