Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of interferon-stimulated genes (ISGs). How asthma-susceptibility genes modulate cellular response upon viral infection by fine-tuning ISG induction and subsequent airway inflammation in genetically susceptible asthma patients remains largely unknown.

To decipher the functions of gasdermin B (encoded by GSDMB) in respiratory virus-induced lung inflammation.

In two independent cohorts, we analysed expression correlation between GSDMB and ISGs. In human bronchial epithelial cell line or primary bronchial epithelial cells, we generated GSDMB-overexpressing and GSDMB-deficient cells. A series of quantitative PCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism of GSDMB for ISG induction. We also generated a novel transgenic mouse line with inducible expression of human unique GSDMB gene in airway epithelial cells and infected the mice with respiratory syncytial virus to determine the role of GSDMB in respiratory syncytial virus-induced lung inflammation in vivo.

GSDMB is one of the most significant asthma-susceptibility genes at 17q21 and acts as a novel RNA sensor, promoting mitochondrial antiviral-signalling protein (MAVS)-TANK binding kinase 1 (TBK1) signalling and subsequent inflammation. In airway epithelium, GSDMB is induced by respiratory viral infections. Expression of GSDMB and ISGs significantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of human GSDMB in mouse airway epithelium led to enhanced ISGs induction and increased airway inflammation with mucus hypersecretion upon respiratory syncytial virus infection.

GSDMB promotes ISGs expression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.

呼吸道病毒引起的炎症是哮喘恶化的主要原因，通常伴随着干扰素刺激基因（ISG）的诱导。在遗传易感哮喘患者中，哮喘易感基因如何通过微调ISG诱导和随后的气道炎症来调节病毒感染后的细胞反应，目前仍不清楚。

破译gasdermin B（由GSDMB编码）在呼吸道病毒引起的肺部炎症中的功能。

在两个独立队列中，我们分析了GSDMB和ISG之间的表达相关性。在人支气管上皮细胞系或原代支气管上皮细胞中，我们产生了GSDMB过度表达和GSDMB缺陷的细胞。进行了一系列定量 PCR、ELISA 和免疫共沉淀测定，以确定GSDMB诱导ISG的功能和机制。我们还培育了一种新型转基因小鼠系，其在气道上皮细胞中诱导表达人类独特的GSDMB基因，并用呼吸道合胞病毒感染小鼠，以确定GSDMB在体内呼吸道合胞病毒诱导的肺部炎症中的作用。

GSDMB是 17q21 上最重要的哮喘易感性基因之一，可作为一种新型 RNA 传感器，促进线粒体抗病毒信号蛋白 (MAVS)-TANK 结合激酶 1 (TBK1) 信号传导和随后的炎症。在气道上皮中，GSDMB是由呼吸道病毒感染诱导的。GSDMB和ISG的表达在两个独立哮喘队列的呼吸道上皮中显着相关。值得注意的是，人GSDMB在小鼠气道上皮中的诱导表达导致ISG诱导增强，呼吸道合胞病毒感染后气道炎症增加，粘液分泌过多。

GSDMB在呼吸道病毒感染时促进ISG表达和气道炎症，从而赋予风险等位基因携带者哮喘风险。