Grant: Travel Awards - Institute Community Support

Asthma is a heterogeneous chronic obstructive lung disorder that is characterized by an invasion of inflammatory cells in the lung. Inhaled corticosteroids are typically used for the treatment of asthma. However, up to 10% of patients can be insensitive to high dose corticosteroids, rendering treatment options ineffective. Among these corticosteroid-insensitive patients, also known as severe asthmatics, a subset has a specific type of lung inflammation caused by inflammatory cells known as neutrophils. Neutrophils are attracted to the lung by Interleukin (IL)-8, a chemokine that is mainly produced by airway epithelial cells. The inflammatory cytokine IL-17A enhances recruitment of neutrophils by inducing the production of IL-8 in bronchial epithelial cells. The implication of IL-17A in provoking corticosteroid insensitivity in severe neutrophilic asthma requires clarification. We hypothesize that IL-17A may decrease the effect of corticosteroids at the transcriptional level. This work will examine the effects of corticosteroids and IL-17A on the regulation of IL-8 in respiratory epithelial cells. First, the primary mechanism underlying IL-17A's ability to decrease corticosteroid sensitivity will be assessed in both cell lines and primary airway epithelial cells from healthy donors and patients with severe neutrophilic asthma. Next, potential therapeutic targets will be identified with the goal to develop targeted therapies that have fewer and less severe side effects. A better understanding of the role of IL-17A on airway epithelial cells in severe neutrophilic asthma will help us develop new personalized therapies.