Arabinogalactan protects mice from allergic asthma via modulation of dendritic cell function

We have previously shown that dust from cowsheds of traditional alpine farms contains substances that protect from experimental allergic lung disease in a mouse model of asthma. Now we present evidence that plant arabinogalactans (AG) are contained in cowshed dust extract (CDE) in high concentration and after isolation show protective activity in vivo. Mice treated with these polysaccharides during sensitization showed dramatically reduced airway eosinophila, IgE production and release of Th2 cytokines. Furthermore, we were able to show that AG as found in cowshed dust is derived from feeding material consisting of a frequent grass species known as Alopecurus pratensis. Inhalation of this molecule also protects from sensitization and allergic airway inflammation, moreover, showing protective activity against hyper reactivity of airways and goblet cell metaplasia. Since control experiments with AG from gum arabic or larch revealed that these molecules exhibit no allergy-protective activity we conclude that this property is a characteristic of AG from grass and not shared by AG from other species. This is likely due to differences in molecular structure as revealed by NMR spectroscopy. Since we have already shown that CDE protects mice by tolerization of dendritic cells we have compared the activity of AG with CDE in a sensitization model using adoptively transferred dendritic cells. Treatment of bone marrow derived dendritic cells with AG resulted in autocrine IL-10 production. Subsequently, in transfer experiments these cells induce limited Th2 responses and as a consequence lung eosinophilia was absent. Interestingly, neutralization of autocrine produced IL-10 partially restored sensitizing capacity of BMDCs. Therefore we conclude that AG acts similar to CDE by tolerizing dendritic cells, thus interfering with their allergy inducing capacity.