IFN-α treatment inhibits induction of type-2 innate lymphoid cell dependent airway hyperresponsiveness

2015-07-20Asthma is a respiratory disease that affects about 300 million people worldwide. Patients with allergic asthma mount an unwanted immune response towards several harmless allergens present in the environment. The immune response towards these allergens, until recently, were thought to be mediated primarily by allergen-specific Th2 cells of the adaptive immune system, through the release of Th2 cytokines like IL-4, IL-5 and IL-13. Recently, Innate Lymphoid Cells 2 (ILC2s) of the innate immune system have been shown to mediate allergic asthma, independently of the adaptive immune system. ILC2s release large amounts of Th2 cytokines (IL-5 and IL-13) in response to IL-33 or IL-25, which are produced by epithelial cells upon exposure to allergens. In this study, we show that IFN-α, a cytokine released during viral infections, inhibits the activation of ILC2s in vitro. Administration of IFN-α prevented the development of ILC2 mediated Airway hyperresponsiveness (AHR) and airway inflammation in mice challenged with either IL-33 or the clinically relevant allergen, Alternaria alternata. Importantly, IFN-α also abrogated the activation of human ILC2s in vitro. Therefore, our findings demonstrate that IFN-α can have potential to be used clinically in patients with allergic asthma. It could also hold promise for treating patients who have severe asthma and are resistant to the current therapies offered