Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation.
Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation.
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DOI：
10.1126/scitranslmed.3009124
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发表时间：
2014-10-01
影响因子：
17.1
通讯作者：
Bartlett NW
中科院分区：
文献类型：
--
作者：
Beale J;Jayaraman A;Jackson DJ;Macintyre JDR;Edwards MR;Walton RP;Zhu J;Man Ching Y;Shamji B;Edwards M;Westwick J;Cousins DJ;Yi Hwang Y;McKenzie A;Johnston SL;Bartlett NW
鼻病毒是病毒诱导的哮喘急性发作的最常见原因，其在与该疾病相关的发病率、死亡率和成本方面继续占最大负担。IL-25激活2型驱动的炎症，在病毒诱导的哮喘急性发作中可能很重要。鼻病毒感染培养的哮喘支气管上皮细胞表现出与供体特应性状态相关的IL-25表达的内在能力提高。在哮喘患者中，在基线和实验性鼻病毒感染期间，体内人IL-25表达更高。在小鼠鼻病毒感染诱导IL-25的表达和增强过敏原诱导的IL-25。IL-25受体的阻断降低了许多RV诱导的急性加重特异性应答，包括2型细胞因子表达、粘液产生和嗜酸性粒细胞、中性粒细胞、嗜碱性粒细胞、T和非T 2型细胞的募集。我们已经确定，哮喘上皮细胞具有增加的内在能力，表达前2型细胞因子，以响应病毒感染，并确定IL-25作为RV诱导的肺部炎症恶化的关键介质。
Rhinoviruses are the most common cause of virally-induced asthma exacerbations which continue to account for the greatest burden in terms of morbidity, mortality and cost associated with this disease. IL-25 activates type-2-driven inflammation and is potentially important in virally-induced asthma exacerbations. Rhinovirus-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 rhinovirus infection. In mice rhinovirus 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, T and non-T type-2 cells. We have identified that asthmatic epithelial cells possess increased intrinsic capacity for expression of a pro-type-2 cytokine in response to a viral infection and identify IL-25 as a key mediator in RV-induced exacerbations of pulmonary inflammation.