IL-33 induces airway inflammation and hyper-responsiveness in respiratory diseases. Although defined as a therapeutic target, there are limited studies that have comprehensively investigated IL-33-mediated responses in the lungs in vivo. In this study, we characterized immunological and physiological responses induced by intranasal IL-33 challenge, in a mouse model. We identified specific cytokines, IL-4, IL-5, IL-6, IL-10, IP-10 and MIP1-α, that are increased in bronchoalveolar lavage and lung tissues by IL-33. Using transcriptomics (RNA-Seq) we demonstrated that 2279 transcripts were up-regulated and 1378 downregulated (≥ 2-fold, p < 0.01) in lung tissues, in response to IL-33. Bioinformatic interrogation of the RNA-Seq data was used to predict biological pathways and upstream regulators involved in IL-33-mediated responses. We showed that the mRNA and protein of STAT4, a predicted upstream regulator of IL-33-induced transcripts, was significantly enhanced in the lungs following IL-33 challenge. Overall, this study provides specific IL-33-induced molecular targets and endpoints that can be used as a resource for in vivo studies, e.g. in preclinical murine models examining novel interventions to target downstream effects of IL-33.

IL-33在呼吸系统疾病中引起气道炎症和反应过度。尽管被定义为治疗目标，但有限的研究已经全面研究了体内肺中IL-33介导的反应。在这项研究中，我们表征了在小鼠模型中鼻内IL-33攻击诱导的免疫和生理反应。我们确定了特定的细胞因子，IL-4，IL-5，IL-6，IL-10，IP-10和MIP1-α，它们在支气管肺泡灌洗和肺组织中被IL-33增加。使用转录组学（RNA-Seq），我们证明了2279个转录本上调，而1378个转录本下调（≥2倍，p <0.01）在肺组织中，对IL-33有反应。RNA-Seq数据的生物信息学调查被用来预测参与IL-33介导的反应的生物途径和上游调节剂。我们显示，STAT4的mRNA和蛋白（IL-33诱导的转录物的预期上游调节剂）在IL-33攻击后在肺中显着增强。总的来说，这项研究提供了特定的IL-33诱导的分子靶点和终点，可以用作体内研究的资源，例如，在临床前小鼠模型中，研究针对IL-33下游效应的新型干预措施。