Defining the effects of IL33 axis genetic variants on viral induced inflammation in asthma

哮喘是一种复杂的呼吸系统疾病，遗传和环境因素都会导致易感性和加重。鼻病毒是病情加重的主要原因；然而，宿主遗传学的贡献和这些过程背后的分子机制并没有很好地定义。鼻病毒诱导支气管上皮细胞释放白细胞介素33 (IL33)，从而激活一系列炎症细胞，从而导致病情恶化。由于IL33和IL33受体（IL1RL1）位点的遗传变异与恶化风险相关，我们假设这些变异可以调节支气管上皮细胞对病毒的反应，以及炎症细胞对IL33的反应最终决定观察到的炎症程度。该项目将结合细胞和分子生物学、免疫学和遗传学来研究上皮细胞-炎症细胞的串扰，并有可能促进我们对尚未满足临床需求的哮喘病毒诱导恶化的理解。

Asthma is a complex respiratory disease, with both genetic and environmental factors contributing to susceptibility and exacerbation. Rhinovirus is a major cause of exacerbations; however the contribution of host genetics and molecular mechanisms underlying these processes and are not well defined. Rhinovirus induces interleukin 33 (IL33) release from bronchial epithelial cells which activates a range of inflammatory cells that drive the exacerbation. As genetic variation in the IL33 and IL33 receptor (IL1RL1) loci have been associated with exacerbation risk we hypothesise that these variants can modulate bronchial epithelial cell responses to virus and how inflammatory cells respond to IL33 ultimately determining the magnitude of inflammation observed. This project will use a combination of cell and molecular biology, immunology and genetics to investigate epithelial cell - inflammatory cell cross talk and has scope to advance our understanding of virus induced exacerbation in asthma where there is an unmet clinical need.