Adenovirus-mediated interleukin-35 gene transfer suppresses allergic airway inflammation in a murine model of asthma.

Abstract

Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. Interleukin (IL)-35 is a recently described member of IL-12 cytokine family that plays a critical role in influencing Th cell differentiation and inflammatory processes. The aim of this study was to examine the effect of adenovirus expressing IL-35 (AdIL-35) on allergic airway hyperresponsiveness (AHR) and inflammation in a mouse model of asthma. BALB/c mice were subjected to an established model of allergic airway disease. AdIL-35 was administered intranasally and the effect of IL-35 on Th2 responses, pulmonary inflammation, goblet cell metaplasia, and AHR were assessed. Transfer of AdIL-35 significantly reduced the severity of AHR and numbers of inflammatory cells and levels of IL-4, IL-5, IL-13, and IL-17 in bronchoalveolar lavage fluid, compared with administration of a control virus. Moreover, AdIL-35 elevated the numbers of CD4+CD25+Foxp3+ regulatory T cells in the lungs. Histological analysis showed that AdIL-35 inhibited allergic lung tissue inflammation and mucus hypersecretion. These results demonstrate that adenovirus-mediated delivery of interleukin-35 gene can mitigate allergic airway inflammation in experimental asthma and suggest that IL-35 may offer a novel therapeutic approach to treat allergic asthma.