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.