Role of IL-17 and IL-23 in the Pathogenesis of Neutrophilic Asthma

Abstract

Asthma is a complex chronic airway disease with several distinct phenotypes characterized by different immunopathological pathways, clinical presentation, physiology, comorbidities, biomarker of allergic inflammation, and response to treatment. Approximately 10% of patients with asthma have severe refractory disease, which is difficult to control on high doses of inhaled corticosteroids and other modifiers. About 50% of these individuals suffer from neutrophilic asthma. Neutrophilic asthma is a phenotype of asthma that is severe and persistent, with frequent exacerbations, and hospitalization. It is characterized by the presence of high levels of neutrophils in the lungs and airways. The IL-23/IL-17 cytokine axis plays an important role in the pathogenesis of neutrophilic asthma. IL-23 is crucial for the differentiation and maintenance of Th17 cells, and it is required for full acquisition of an effector function of Th17 cells. Furthermore, IL-23 prolongs the expression of Th17 cytokines, such as IL-17, IL-17F, IL-22, and GM-CSF which induce tissue pathology and chronic inflammatory diseases. Th17 cells produce IL-17 which plays a key role in the pathogenesis of neutrophilic asthma by expressing the secretion of chemoattractant, cytokines, and chemokines which lead to the recruitment, and activation of neutrophils. Activated neutrophils release multiple proteinases, cytokines, chemokines, and reactive oxygen species which cause airway epithelial cell injury, inflammation, hyperresponsiveness, and airway remodeling. Neutrophilic asthma is unresponsive to high dose inhaled corticosteroids, and probably to novel monoclonal antibody therapies. There is need for targeted precision biologics, and other treatment modalities for these patients, such as macrolide antibiotics, and bronchial thermoplasty.