Beale Janine, Jayaraman Annabelle, Jackson David J, Macintyre Jonathan D R, Edwards Michael R, Walton Ross P, Zhu Jie, Man Ching Yee, Shamji Betty, Edwards Matt, Westwick John, Cousins David J, Yi Hwang You, McKenzie Andrew, Johnston Sebastian L, Bartlett Nathan W
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
Sci Transl Med. 2014 Oct 1;6(256):256ra134. doi: 10.1126/scitranslmed.3009124.
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.
鼻病毒（RVs）是病毒诱发哮喘加重的最常见原因，在发病率、死亡率及相关费用方面，它是哮喘负担的重要组成部分。白细胞介素-25（IL-25）可激活2型驱动的炎症反应，因此在病毒诱发的哮喘加重中可能具有重要作用。为对此进行研究，我们检测了RV诱导的IL-25是否会导致哮喘加重。感染RV的培养哮喘支气管上皮细胞表现出更高的IL-25表达内在能力，这与供体的特应性状态相关。在体内，哮喘患者在基线期和实验性RV感染期间的人IL-25表达更高。此外，在小鼠中，RV感染诱导IL-25表达并增强变应原诱导的IL-25。阻断IL-25受体可减少许多RV诱导的加重特异性反应，包括2型细胞因子表达、黏液分泌以及嗜酸性粒细胞、中性粒细胞、嗜碱性粒细胞、T细胞和非T 2型细胞的募集。因此，哮喘上皮细胞在病毒感染时表达促2型细胞因子的内在能力增强，且IL-25是RV诱导的肺部炎症加重的关键介质。
