Activation of Th17-immune response in a mouse model of neutrophilic asthma

• Igor P. Shilovskiy
• Aleksandr A. Nikolskii
• Valeriia I. Kovchina
• Bolotova S.I.
• Liudmila I. Vishniakova
• Sokolova A.R.
• Ekaterina D. Barvinskaia
• Musa R. Khaitov

Abstract

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the respiratory tract. The majority of patients with mild to moderate BA are well respond to corticosteroid treatment. However, there is a group of patients (up to 10% of BA cases) with severe BA which resistant to conventional corticosteroid therapy. A detailed study of this phenomenon revealed a relationship between the severity of BA, activation of Th1- and Th17-immune responses and neutrophilic type of inflammation. At the same time patients with Th2-mediated eosinophilic pulmonary inflammation respond to corticosteroids well. In order to understand the mechanisms of corticosteroid resistance we developed a model of BA in mice with a predominant neutrophilic rather than eosinophilic type of inflammation. BALB/c mice were immunized with the mixture of the ovalbumin allergen and Freund’s adjuvant, followed by aerosol challenge with the same allergen mixed with E. coli lipopolysaccharide. As a result, mice developed key manifestations of neutrophilic BA: production of allergen-specific IgE antibodies, development of bronchial hyperreactivity, remodeling of the respiratory tract and infiltration of lung tissue with neutrophils. Moreover, the development of this pathology was Th17-dependent, that corresponds to the clinical observations in human. The presented model of neutrophilic BA in mice can be used both for studying the pathogenesis of the disease, and for testing new approaches to its therapy.

Keywords:bronchial asthma; mouse model; Th17-immune response

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