Mechanistic Investigation of Gut Mycobiota in the Regulation of Lung Immunity and Disease

肠道真菌群调节肺免疫与疾病的机制研究(PA-20-188) 项目摘要/摘要 哮喘是一种常见的慢性呼吸道炎症，影响着大约2500万美国人和3.34亿人 世界各地的人们。在哺乳动物的肠道中，一个多样化的真菌群落，称为真菌生物群，形成了当地和 全身性宿主免疫反应。肠道真菌群落的改变与 炎症性疾病，如哮喘、慢性阻塞性肺疾病(COPD)和炎症性肠病 疾病(IBD)。我们最近的发现表明，肠道特化吞噬细胞可能介导了这种激活。 在过敏性呼吸道疾病期间真菌刺激的T细胞。尽管如此，肠肺的确切机制 免疫串扰是未知的。根据这些初步发现，我们推测肠道共生真菌 启动抗真菌免疫，影响肺部免疫，调节呼吸道炎症进程。 这个项目的目标是了解肠道真菌和宿主之间的分子和细胞相互作用。 肺免疫，特别是T细胞。虽然目前的提议是为了阐明肠道的基本影响 真菌对肺部免疫和疾病的影响，并揭示肠道启动的抗真菌T细胞的机制 活化和迁移在免疫介导的呼吸道炎症发展中的作用。我的长期目标是 研究肠道共生真菌区系如何调节肠道-系统轴并影响其他肺脏 疾病，如慢性阻塞性肺病和囊性纤维化。在我的K99训练期间，我将由一支 在真菌区系、粘膜免疫学、T细胞生物学和肺病方面有专长的导师和科学顾问 疾病。他们将在研究和职业过渡方面提供强有力的支持和指导 独立性，并帮助我发展必要的技术技能和肺部免疫的概念性知识 和抗真菌T细胞。这个K99/R00奖项将使我能够获得深入分析所需的技能 以及对肠道-全身轴的了解，目标是创造治疗哮喘、COPD、CF、 以及其他与免疫相关的肺部疾病。

Mechanistic Investigation of Gut Mycobiota in the Regulation of Lung Immunity and Disease (PA-20-188) Project summary/Abstract Asthma is a common, chronic airway inflammation that affects around 25 million Americans and 334 million people worldwide. In the mammalian gut, a diverse fungal community, known as the mycobiota shapes local and systemic host immune responses. Alterations of the gut fungal community are strongly associated with inflammatory disorders such as asthma, chronic obstructive pulmonary disease (COPD), and inflammatory bowel diseases (IBD). Our recent findings suggest that intestinal specialized phagocytes could mediate the activation of fungal-primed T cells during allergic airway disease. Despite these, the precise mechanisms of gut- lung immune crosstalk are unknown. Based on these preliminary findings, we hypothesize that gut commensal fungi initiate antifungal immunity that affects lung immunity and modulates the progression of airway inflammation. The objectives of this project are to understand the molecular and cellular interplay between gut fungi and host lung immunity with specific focus on T cells. While the current proposal is to illuminate the basic effects of gut fungi on lung immunity and disease and to uncover mechanistic insights about gut-primed antifungal T cell activation and migration on the development of immune-mediated airway inflammation. My long-term goal is to investigate how the gut commensal mycobiota modulates the gut-systemic axis and impacts other pulmonary diseases, such as COPD and cystic fibrosis (CF). During my K99 training, I will be supervised by a team of mentors and scientific advisors with expertise in mycobiota, mucosal immunology, T cell biology and pulmonary diseases. They will provide strong support and mentorship in both research and career transition to independence, and help me to develop necessary technical skills and conceptual knowledge on lung immunity and antifungal T cells. This K99/R00 award will enable me to acquire the skills necessary for a deep analysis and understanding of the gut-systemic axis with the goal of creating novel therapies to treat asthma, COPD, CF, and other immune-related pulmonary diseases.