ИСТИНА

Asthma is a common inflammatory disease of the airway, which is caused by a combination of genetic and environmental factors, and is characterized by airflow obstruction, wheezing, eosinophilia and neutrophilia of lungs and sputum. IL-6 is implicated in the regulation of both protective and pathogenic responses in the lung, however, its role in allergic lung inflammation and critical IL-6 producing cellular sources remain unclear. To elucidate critical IL-6-producing cells in pathogenesis of allergic airway inflammation, we generated mice with specific inactivation of IL-6 in CD11c-expressing dendritic cells (DCs) or lysozyme-expressing myeloid cells (predominantly macrophages and neutrophils)and subjected them to intranasal administration of HDM (house dust mite) extract for 5 days a week with sensitization treatment one week prior to the main course. We show that complete genetic inactivation of IL-6 or pharmacological inhibition using blocking antibody ameliorated the disease with significant decrease in eosinophilia of the lungs. Moreover, we demonstrate that IL-6 from both CD11c-expressing DCs cells and lysozyme-expressing myeloid cells distinctly contributes to the disease. Specific deletion of IL-6 in dendritic cells reduced key indicators of allergic inflammation including lymphocyte infiltration, eosinophil and Th2 cell accumulation in the lungs, and expression of asthma-associated inflammatory mediators but no effect on IgE levels. In contrast, macrophage-derived IL-6 deficiency exhibited attenuated IgE production. These results suggest that IL-6 plays a pathogenic role in HDM-induced asthma model and that both lung macrophages and dendritic cells provide the considerable source of IL-6 and distinctly contribute to the disease. The evaluation of relative contribution of IL-6 from dendritic cells and macrophages to the disease is underway. The work was supported by the Russian Science Foundation, grant No. 14-25-00160.