Investigation of the Role(s) of the Neurotrophins GDNF and Neurturin in Allergic Asthma in Mouse Models - GDNF

Coordinating Institution: CRP Sante
Contracting Partner(s): University of Helsinki (Finland)
From: 01/01/2008
To: 31/12/2009
Budget: 287,500.00€
Contact(s): Zimmer Jacques

Summary

Allergic asthma is characterised by chronic inflammation of the bronchial tree triggered by inhaled allergens. This leads to hypersecretion, bronchoconstriction and ultimately to respiratory insufficiency. While IgE mediated allergic reactions are relatively well understood, we know much less about the relationship between airway inflammation and changes in lung function. Several studies have shown that neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are implicated in the pathogenesis of many features and symptoms of asthma.

Neurotrophins were previously described as factors influencing the development, function and survival of nerves. Furthermore various cell types outside the nervous system, including immune cells and structural tissue cells, were identified as potential sources and targets of neurotrophins. Recently, eosinophils were identified as a source of NGF present in the late allergic response. Murine models help in elucidating the pathogenesis of allergic asthma and the evaluation of new therapeutic strategies. In animal models, NGF was able to mimic bronchial hyperresponsiveness and airway inflammation, which are characteristic features in asthma.

By using a C57BL/6 (B6) mouse model, we observed the influence of another neurotrophin, neurturin (NTN) on airway inflammation. In our model, we compared the inflammatory response in NTN-KO mice and in GFRalpha2-KO mice with the wild type mice. We have shown an increase of Th2 cytokines and eosinophilic airway inflammation in NTN-KO mice. Furthermore, we observed mRNA expression of GFRalpha2, the NTN receptor, in different types of cells present in lung and lymph node tissues. Our aims are to determine the source and the regulation of NTN and GFRalpha2 in the airways.

Figure: Lung Histology