Targeting IRF7 asthma phenotypes through immuno-modulation therapy

Viral-induced severe asthma exacerbations in children are characterized by IRF7hi and IRF7lo molecular phenotypes. We have developed an experimental animal model that mirrors these response patterns in asthma-resistant PVG and asthma-susceptible BN rats respectively. We aimed to i) characterize the immunological and molecular hallmarks of PVG and BN responses to virus/allergen exposure, and (ii) evaluate the utility of innate immune training with the bacterial lysate OM85 to attenuate ensuing inflammation. Animals were sensitized to OVA/alum, inoculated with murine-adapted Rhinovirus model (vMC0), and challenged with OVA 24h later. RNA-seq was performed on lung and bone marrow at several time points post virus/allergen exposure.儿童病毒诱导的重度哮喘急性加重以干扰素调节因子7（Interferon Regulatory Factor 7，IRF7）高表达（IRF7hi）与低表达（IRF7lo）的分子表型为特征。本研究建立了实验动物模型，可分别模拟哮喘抵抗型PVG与哮喘易感型BN大鼠的上述免疫应答模式。本研究旨在实现两大目标：其一，解析PVG与BN大鼠在病毒/过敏原暴露后的免疫学与分子生物学特征；其二，评估采用细菌裂解物OM85进行先天免疫训练以减轻后续炎症的应用潜力。实验动物经卵清蛋白（Ovalbumin，OVA）/铝佐剂致敏后，接种鼠适应性鼻病毒模型（vMC0），并于24小时后以OVA激发。于病毒/过敏原暴露后的多个时间点采集肺组织与骨髓样本，开展RNA测序（RNA-seq）分析。