PT - JOURNAL ARTICLE AU - Beale, Janine AU - Jayaraman, Annabelle AU - Jackson, David J. AU - Macintyre, Jonathan D. R. AU - Edwards, Michael R. AU - Walton, Ross P. AU - Zhu, Jie AU - Ching, Yee Man AU - Shamji, Betty AU - Edwards, Matt AU - Westwick, John AU - Cousins, David J. AU - Hwang, You Yi AU - McKenzie, Andrew AU - Johnston, Sebastian L. AU - Bartlett, Nathan W. TI - Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation AID - 10.1126/scitranslmed.3009124 DP - 2014 Oct 01 TA - Science Translational Medicine PG - 256ra134--256ra134 VI - 6 IP - 256 4099 - http://stm.sciencemag.org/content/6/256/256ra134.short 4100 - http://stm.sciencemag.org/content/6/256/256ra134.full AB - Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. Interleukin-25 (IL-25) activates type 2–driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we examined whether RV-induced IL-25 could contribute to asthma exacerbations. RV-infected cultured asthmatic bronchial epithelial cells exhibited a heightened intrinsic capacity for IL-25 expression, which correlated with donor atopic status. In vivo human IL-25 expression was greater in asthmatics at baseline and during experimental RV infection. In addition, in mice, RV infection induced IL-25 expression and augmented allergen-induced IL-25. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. Therefore, asthmatic epithelial cells have an increased intrinsic capacity for expression of a pro–type 2 cytokine in response to a viral infection, and IL-25 is a key mediator of RV-induced exacerbations of pulmonary inflammation.