病毒感染和STING相关信号通路在特发性肺纤维化急性加重中的作用及机制研究

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a fatal condition with high mortality (over 80%). Its etiology and pathogenesis remain unknown. There is a lack of effective treatment for it. Based on our long-term clinical observation, most cases of AE-IPF are induced by "cold" and developed very rapidly similar to the acute respiratory distress syndrome (ARDS). We found high detection rates of virus in AE-IPF patients. The immune response in AE-IPF was abnormal. STING signaling pathway were different in AE-IPF compared with stable IPF. Which pathogens are critical for triggering AE-IPF? Why AE-IPF patients are so hypersensitive to "cold"? What are the immunologic and pathological mechanisms of their lung lesions after patients are exposed to "cold"? What’s the mechanism of STING signaling pathway in virus-induced AE-IPF? All the above questions are yet to be explained clearly. In the current study we will utilize advanced technological methods including clinical samples, animal model, cell line and molecular to search for key pathogens for AE-IPF, analyze immunologic characteristics of IPF/AE-IPF patients, and investigate the mechanism of STING signaling pathway in virus-induced AE-IPF. This study will provide insights and new treatment for AE-IPF, which has significant value for translational and clinical medicine.

特发性肺纤维化（IPF)急性加重(AE-IPF)病死率高达80%以上。病因和发生机制不清，缺乏有效治疗方法。临床观察发现AE-IPF患者多因“感冒”诱发肺内病灶快速进展，如同急性呼吸窘迫综合征(ARDS)。还发现AE-IPF患者体内病毒检出率显著增高，免疫功能明显失衡，STING及其信号通路变化不同于稳定期患者。究竟哪些“感冒”病毒是AE-IPF最主要的触发因素？IPF/AE-IPF患者免疫功能发生了什么变化使其特别容易“感冒”并迅速进展至“ARDS”？STING及其相关通路在其中发挥了何种作用？都是急待回答的科学问题。本项目从临床、动物模型、细胞和分子多层面研究，力图确定与AE-IPF密切相关的病毒，分析IPF/AE-IPF患者免疫功能变化特征，阐明STING及其通路在病毒感染引起AE-IPF中的免疫调控机制，为探索AE-IPF防治新靶标和新策略奠定基础，具有重要的转化医学理论及临床意义

特发性肺纤维化(IPF)急性加重(AE-IPF)病死率高达80%以上。病因和发生机制不清，缺乏有效治疗方法。临床观察发现AE-IPF患者多因“感冒”诱发肺内病灶快速进展，如同急性呼吸窘迫综合征(ARDS)。还发现AE-IPF患者体内病毒检出率显著增高，免疫功能明显失衡，STING及其信号通路变化不同于稳定期患者。究竟哪些“感冒”病毒是AE-IPF最主要的触发因素？IPF/AE-IPF患者免疫功能发生了什么变化使其特别容易“感冒”并迅速进展至“ARDS”？STING及其相关通路在其中发挥了何种作用？都是急待回答的科学问题。本项目从临床、动物模型、细胞和分子多层面研究，力图确定与AE-IPF密切相关的病毒，分析IPF/AE-IPF患者免疫功能变化特征，阐明STING及其通路在病毒感染引起AE-IPF中的免疫调控机制。项目负责人以通讯作者发表标注项目资助号的SCI论文12篇；授权发明专利3项（国内2项，国际1项），软件著作权登记1项；培养研究生10人。项目成果有望转化为实际临床应用，将加深我们对特发性肺纤维化及急性加重的发病机制的了解，而且可为临床治疗提供理论及实验依据；综上，本项目成果可为探索AE-IPF防治新靶标和新策略奠定基础，有望应用于肺纤维化急性加重以及肺损伤等领域的临床治疗，具有重要的转化医学理论及临床意义。