IFNγ-mediated IL-33 production is dependent on the aryl hydrocarbon receptor in human bronchial epithelial cells.

IL-33 is an alarmin produced by stromal cells and is known to promote airway inflammation. IL-33 is a critical mediator of steroid-unresponsiveness in severe asthma. We have previously shown that IFNγ, a cytokine known to be elevated in airway inflammation and severe asthma, enhances the abundance of IL-33 in bronchial epithelial cells. Previous studies have shown that environmental insults such as particulate matter results in activation of the aryl hydrocarbon receptor (AhR) and IL-33 production. However, the role of AhR in cytokine-mediated IL-33 production is unknown. In this study, we demonstrate that the knockdown of AhR results in significant decrease in IFNγ-mediated IL-33 production and phosphorylation of STAT1 (Y701), in human bronchial epithelial cells. The findings of this report suggest that AhR may be an essential component in IFNγ-mediated IL-33 production in the lungs.